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Volume 16, Issue 2 (Jun 2011)

The role of P63 in cancer, stem cells and cancer stem cells

Marta Nekulova
  • Masaryk Memorial Cancer Institute
  • Email:
/ Jitka Holcakova
  • Masaryk Memorial Cancer Institute
  • Email:
/ Philip Coates
  • University of Dundee
  • Email:
/ Borivoj Vojtesek
  • Masaryk Memorial Cancer Institute
  • Email:
Published Online: 2011-03-26 | DOI: https://doi.org/10.2478/s11658-011-0009-9


The transcription factor p63 has important functions in tumorigenesis, epidermal differentiation and stem cell self-renewal. The TP63 gene encodes multiple protein isoforms that have different or even antagonistic roles in these processes. The balance of p63 isoforms, together with the presence or absence of the other p53 family members, p73 and p53, has a striking biological impact. There is increasing evidence that interactions between p53-family members, whether cooperative or antagonistic, are involved in various cell processes. This review summarizes the current understanding of the role of p63 in tumorigenesis, metastasis, cell migration and senescence. In particular, recent data indicate important roles in adult stem cell and cancer stem cell regulation and in the response of cancer cells to therapy.

Keywords: p63; TAp63; ΔNp63; p53 family; Cancer; Stem cells

  • [1] Kaghad, M., Bonnet, H., Yang, A., Creancier, L., Biscan, J.C., Valent, A., Minty, A., Chalon, P., Lelias, J.M., Dumont, X., Ferrara, P., McKeon, F. and Caput, D. Monoallelically expressed gene related to p53 at 1p63, a region frequently deleted in neuroblastoma and other human cancers. Cell 90 (1997) 809–819. [Crossref]

  • [2] Yang, A.N., Kaghad, M., Wang, Y.M., Gillett, E., Fleming, M.D., Dotsch, V., Andrews, N.C., Caput, D. and McKeon, F. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol. Cell 2 (1998) 305–316. [Crossref]

  • [3] Joerger, A.C., Rajagopalan, S., Natan, E., Veprintsev, D.B., Robinson, C.V. and Fersht, A.R. Structural evolution of p53, p63, and p73: Implication for heterotetramer formation. Proc. Natl. Acad. Sci. USA 106 (2009) 17705–17710. [Crossref]

  • [4] Stifanic, M., Micic, M., Ramsak, A., Blaskovic, S., Ruso, A., Zahn, R. and Batel, R. p63 in Mytilus galloprovincialis and p53 family members in the phylum Mollusca. Comp. Biochem. Physiol. B. Biochem. Mol. Biol. 154 (2009) 264–273. [Crossref]

  • [5] Dohn, M., Zhang, S.Z. and Chen, X.B. p63 alpha and Delta Np63 alpha can induce cell cycle arrest and apoptosis and differentially regulate p53 target genes. Oncogene 20 (2001) 3193–3205. [Crossref]

  • [6] Wu, G., Nomoto, S., Hoque, M., Dracheva, T., Osada, M., Lee, C., Dong, S., Guo, Z., Benoit, N., Cohen, Y., Rechthand, P., Califano, J., Moon, C.S., Ratovitski, E., Jen, J., Sidransky, D. and Trink, B. Delta Np63 alpha and TAp63 alpha regulate transcription of genes with distinct biological functions in cancer and development. Canc. Res. 63 (2003) 2351–2357.

  • [7] Osada, M., Park, H.L., Nagakawa, Y., Yamashita, K., Fomenkov, A., Kim, M.S., Wu, G.J., Nomoto. S., Trink, B. and Sidransky D. Differential recognition of response elements determines target gene specificity for p53 and p63. Mol. Cell. Biol. 25 (2005) 6077–6089. [Crossref]

  • [8] Testoni, B., Borrelli, S., Tenedini, E., Alotto, D., Castagnoli, C., Piccolo, S., Tagliafico, E., Ferrari, S., Vigano, M.A. and Mantovani R. Identification of new p63 targets in human keratinocytes. Cell Cycle 5 (2006) 2805–2811. [Crossref]

  • [9] Yang, A., Zhu, Z., Kapranov, P., McKeon, F., Church, G.M., Gingeras, T.R. and Struhl, K. Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells. Mol. Cell 24 (2006) 593–602. [Crossref]

  • [10] Vigano, M.A., Lamartine, J., Testoni, B., Merico, D., Alotto, D., Castagnoli, C., Robert, A., Candi, E., Melino, G., Gidrol, X. and Mantovani, R. New p63 targets in keratinocytes identified by a genome-wide approach. EMBO J. 25 (2006) 5105–5116. [Crossref]

  • [11] Mangiulli, M., Valletti, A., Caratozzolo, M.F., Tullo, A., Sbisa, E., Pesole, G. and D’Erchia, A.M. Identification and functional characterization of two new transcriptional variants of the human p63 gene. Nucl. Acid. Res. 37 (2009) 6092–6104. [Crossref]

  • [12] Thanos, C.D. and Bowie, J.U. p53 Family members p63 and p73 are SAM domain-containing proteins. Prot. Sci. 8 (1999) 1708–1710. [Crossref]

  • [13] Serber, Z., Lai, H.C., Yang, A., Ou, H.D., Sigal, M.S., Kelly, A.E., Darimont, B.D., Duijf, P.H.G., van Bokhoven, H., McKeon, F. and Dötsch, V. A C-terminal inhibitory domain controls the activity of p63 by an intramolecular mechanism. Mol. Cell. Biol. 22 (2002) 8601–8611. [Crossref]

  • [14] Sayan, B.S., Sayan, A.E., Yang, A.L., Aqeilan, R.I., Candi, E., Coher, G.M., Knight, R.A., Croce, C.M. and Melino, G. Cleavage of the transactivationinhibitory domain of p63 by caspases enhances apoptosis. Proc. Natl. Acad. Sci. USA 104 (2007) 10871–10876. [Crossref]

  • [15] Ghioni, P., Bolognese, F., Duijf, P.H.G., van Bokhoven, H., Mantovani, R. and Guerrini, L. Complex transcriptional effects of p63 isoforms: Identification of novel activation and repression domains. Mol. Cell. Biol. 22 (2002) 8659–8668. [Crossref]

  • [16] Helton, E.S., Zhu, J.H. and Chen, X.B. The unique NH2-terminally deleted (Delta N) residues, the PXXP motif, and the PPXY motif are required for the transcriptional activity of the Delta N variant of p63. J. Biol. Chem. 281 (2006) 2533–2542.

  • [17] Nylander, K., Vojtesek, B., Nenutil, R., Lindgren, B., Roos, G., Wang, Z.X., Sjostrom, B., Dahlqvist, A. and Coates, P.J. Differential expression of p63 isoforms in normal tissues and neoplastic cells. J. Pathol. 198 (2002) 417–427.

  • [18] Reis-Filho, J.S., Torio, B., Albergaria, A. and Schmitt, F.C. p63 expression in normal skin and usual cutaneous carcinomas. J. Cutan. Pathol. 29 (2002) 517–523. [Crossref]

  • [19] Di Como, C.J., Urist, M.J., Babayan, I., Drobnjak, M., Hedvat, C.V., Teruya-Feldstein, J., Pohar, K., Hoos, A. and Cordon-Cardo, C. p63 expression profiles in human normal and tumor tissues. Clin. Canc. Res. 8 (2002) 494–501.

  • [20] Rosenbluth, J.M., Johnson, K., Tang, L.J., Triplett, T. and Pietenpol, J.A. Evaluation of p63 and p73 antibodies for cross-reactivity. Cell Cycle 8 (2009) 3702–3706. [Crossref]

  • [21] Hedvat, C.V., Teruya-Feldstein, J., Puig, P., Capodieci, P., Dudas, M., Pica, N., Qin, J., Cordon-cardo, C. and Di Como, C.J. Expression of p63 in diffuse large B-cell lymphoma. Appl. Immunohistochem. Mol. Morphol. 13 (2005) 237–242. [Crossref]

  • [22] Livera, G., Petre-Lazar, B., Guerquin, M.J., Trautmann, E., Coffigny, H. and Habert, R. p63 null mutation protects mouse oocytes from radio-induced apoptosis. Reproduction 135 (2008) 3–12. [Crossref]

  • [23] Suh, E.K., Yang, A., Kettenbach, A., Bamberger, C., Michaelis, A.H., Zhu, Z., Elvin, J.A., Bronson, R.T., Crum, C.P. and McKeon, F. p63 protects the female germ line during meiotic arrest. Nature 444 (2006) 624–628.

  • [24] Nishi, H., Isaka, K., Sagawa, Y., Usuda, S., Fujito, A., Ito, H., Senoo, M., Kato, H. and Takayama, M. Mutation and transcription analyses of the p63 gene in cervical carcinoma. Int. J. Oncol. 15 (1999) 1149–1153.

  • [25] Wang, T.Y., Chen, B.F., Yang, Y.C., Chen, H., Wang, Y., Cviko, A., Quade, B.J., Sun, D., Yang, A., McKeon, F.D. and Crum, C.P. Histologic and immunophenotypic classification of cervical carcinomas by expression of the p53 homologue p63: a study of 250 cases. Hum. Pathol. 32 (2001) 479–486. [Crossref]

  • [26] Idrees, M.T., Schlosshauer, P., Li, G. and Burstein, D.E. GLUT1 and p63 expression in endometrial intraepithelial and uterine serous papillary carcinoma. Histopathology 49 (2006) 75–81. [Crossref]

  • [27] Ito, Y., Takeda, T., Wakasa, K., Tsujimoto, M., Sakon, M. and Matsuura, N. Expression of p73 and p63 proteins in pancreatic adenocarcinoma: p73 overexpression is inversely correlated with biological aggressiveness. Int. J. Mol. Med. 8 (2001) 67–71.

  • [28] Harmes, D.C., Bresnick, E., Lubin, E.A., Watson, J.K., Heim, K.E., Curtin, J.C., Suskind, A.M., Lamb, J. and DiRenzo, J. Positive and negative regulation of Delta N-p63 promoter activity by p53 and Delta N-p63-alpha contributes to differential regulation of p53 target genes. Oncogene 22 (2003) 7607–7616. [Crossref]

  • [29] Weinstein, M.H., Signoretti, S. and Loda, M. Diagnostic utility of immunohistochemical staining for p63, a sensitive marker of prostatic basal cells. Mod. Pathol. 15 (2002) 1302–1308. [Crossref]

  • [30] Chen, B.Y., Liu, J.Y., Chang, H.H., Chang, C.P., Lo, W.Y., Kuo, W.H., Yang, C.R. and Lin, D. Hedgehog is involved in prostate basal cell hyperplasia formation and its progressing towards tumorigenesis. Biochem. Biophys. Res. Commun. 357 (2007) 1084–1089.

  • [31] Glickman, J.N., Yang, A., Shahsafaei, A., McKeon, F. and Odze, R.D. Expression of p53-related protein p63 in the gastrointestinal tract and in esophageal metaplastic and neoplastic disorders. Hum. Pathol. 32 (2001) 1157–1165. [Crossref]

  • [32] Basturk, O., Khanani, F., Sarkar, F., Levi, E., Cheng, J.D. and Adsay, N.V. DeltaNp63 expression in pancreas and pancreatic neoplasia. Mod. Pathol. 18 (2005) 1193–1198. [Crossref]

  • [33] Koga, F., Kawakami, S., Fujii, Y., Saito, K., Ohtsuka, Y., Iwai, A., Ando, N., Takizawa, T., Kageyama, Y. and Kihara, K. Impaired p63 expression associates with poor prognosis and uroplakin III expression in invasive urothelial carcinoma of the bladder. Clin. Cancer Res. 9 (2003) 5501–5507.

  • [34] Urist, M.J., Di Como, C.J., Lu, M.L., Charytonowicz, E., Verbel, D., Crum, C.P., Ince, T.A., McKeon, F.D. and Cordon-Cardo, C. Loss of p63 expression is associated with tumor progression in bladder cancer. Am. J. Pathol. 161 (2002) 1199–1206.

  • [35] Park, B.J., Lee, S.J., Kim, J.I., Lee, S.J., Lee, CH., Chang, S.G., Park, J.H. and Chi, S.G. Frequent alteration of p63 expression in human primary bladder carcinomas. Cancer Res. 60 (2000) 3370–3374.

  • [36] Koga, F., Kawakami, S., Kumagai, J., Takizawa, T., Ando, N., Arai, G., Kageyama, Y. and Kihara, K. Impaired Delta Np63 expression assocites with reduced beta-catenin and aggressive phenotypes of urothelial neoplasms. Br. J. Cancer. 88 (2003) 740–747. [Crossref]

  • [37] Yamaguchi, K., Wu, L., Caballero, O.L., Hibi, K., Trink, B., Resto, V., Cairns, P., Okami, K., Koch, W.M., Sidransky, D. and Jen, J. Frequent gain of the p40/p51/p63 gene locus in primary head and neck squamous cell carcinoma. Int. J. Cancer 86 (2000) 684–689. [Crossref]

  • [38] Thurfjell, N., Coates, P.J., Uusitalo, T., Mahani, D., Dabelsteen, E., Dahlqvist, A., Sjöström, B., Roos, G. and Nylander, K. Complex p63 mRNA isoform expression patterns in squamous cell carcinoma of the head and neck. Int. J. Oncol. 25 (2004) 27–35.

  • [39] Zangen, R., Ratovitski, E. and Sidransky, D. DeltaNp63alpha levels correlate with clinical tumor response to cisplatin. Cell Cycle 4 (2005) 1313–1315. [Crossref]

  • [40] Tannapfel, A., Schmelzer, S., Benicke, M., Klimpfinger, M., Kohlhaw, K., Mössner, J., Engeland, K. and Wittekind, C. Expression of the p53 homologues p63 and p73 in multiple simultaneous gastric cancer. J. Pathol. 195 (2001) 163–170.

  • [41] Massion, P.P., Taflan, P.M., Jamshedur Rahman, S.M., Yildiz, P., Shyr, Y., Edgerton, M.E., Westfall, M.D., Roberts, J.R., Pietenpol, J.A., Carbone, D.P. and Gonzalez, A.L. Significance of p63 amplification and overexpression in lung cancer development and prognosis. Cancer Res. 63 (2003) 7113–7121.

  • [42] Wang, B.Y., Gil, J., Kaufman, D., Gan, L., Kohtz, D.S. and Burstein, D.E. P63 in pulmonary epithelium, pulmonary squamous neoplasms, and other pulmonary tumors. Hum. Pathol. 33 (2002) 921–926. [Crossref]

  • [43] Ying, H., Chang, D.L., Zheng, H., McKeon, F. and Xiao, Z.X. DNA-binding and transactivation activities are essential for TAp63 protein degradation. Mol. Cell. Biol. 25 (2005) 6154–6164. [Crossref]

  • [44] Osada, M., Inaba, R., Shinohara, H., Hagiwara, M., Nakamura, M. and Ikawa, Y. Regulatory domain of protein stability of human P51/TAP63, a P53 homologue. Biochem. Biophys. Res. Commun. 283 (2001) 1135–1141.

  • [45] Ghioni, P., D’Alessandra, Y., Mansueto, G., Jaffray, E., Hay, R.T., La Mantia, G. and Guerrini, L. The protein stability and transcriptional activity of p63 alpha are regulated by SUMO-1 conjugation. Cell Cycle 4 (2005) 183–190.

  • [46] Petitjean, A., Ruptier, C., Tribollet, V., Hautefeuille, A., Chardon, F., Cavard, C., Puisieux, A., Hainaut, P. and de Fromentel, C.C. Properties of the six isoforms of p63: p53-like regulation in response to genotoxic stress and cross talk with Delta Np73. Carcinogenesis 29 (2008) 273–281. [Crossref]

  • [47] MacPartlin, M., Zeng, S., Lee, H., Stauffer, D., Jin, Y., Thayer, M. and Lu, H. p300 regulates p63 transcriptional activity. J. Biol. Chem. 280 (2005) 30604–30610.

  • [48] Fomenkov, A., Zangen, R., Huang, Y.P., Osada, M., Guo, Z., Fomenkov, T., Trink, B., Sidransky, D. and Ratovitski, E.A. RACK1 and stratifin target DeltaNp63alpha for a proteasome degradation in head and neck squamous cell carcinoma cells upon DNA damage. Cell Cycle 3 (2004) 1285–1295. [Crossref]

  • [49] Chatterjee, A., Chang, X., Sen, T., Ravi, R., Bedi, A. and Sidransky, D. Regulation of p53 family member isoform ΔNp63α by the nuclear factor-κB targeting kinase IκB kinase β. Cancer Res. 70 (2010) 1419–1429. [Crossref]

  • [50] Wang, N., Guo, L., Rueda, B.R. and Tilly, J.L. Cables1 protects p63 from proteasomal degradation to ensure deletion of cells after genotoxic stress. EMBO J. 11 (2010) 633–639. [Crossref]

  • [51] Tomlinson, V., Gudmundsdottir, K., Luong, P., Leung, K.-Y., Knebel, A. and Basu, S. JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis. Cell Death Dis. 1,e29 (2010) doi:10.1038/cddis.2010.7.

  • [52] Kadakia, M., Slader, C. and Berberich, S.J. Regulation of p63 function by Mdm2 and MdmX. DNA Cell Biol. 20 (2001) 321–330. [Crossref]

  • [53] Little, N.A. and Jochemsen, A.G. Hdmx and Mdm2 can repress transcription activation by p53 but not by p63. Oncogene 20 (2001) 4576–4580. [Crossref]

  • [54] Calabro, V., Mansueto, G., Parisi, T., Vivo, M., Calogero, R.A. and La Mantia, G. The human MDM2 oncoprotein increases the transcriptional activity and the protein level of the p53 homolog p63. J. Biol. Chem. 277 (2002) 2674–2681.

  • [55] Galli, F., Rossi, M., D’Alessandra, Y., De Simone, M., Lopardo, T., Haupt, Y., Alsheich-Bartok, O., Anzi, S., Shaulian, E., Calabro, V., La Mantia, G. and Guerrini, L. MDM2 and Fbw7 cooperate to induce p63 protein degradation following DNA damage and cell differentiation. J. Cell. Sci. 123 (2010) 2423–2433. [Crossref]

  • [56] Lin, Y.L., Sengupta, S., Gurdziel, K., Bell, G.W., Jacks, T. and Flores, E.R. p63 and p73 transcriptionally regulate genes involved in DNA repair. PLoS Genet. 5 (2009) e1000680. [Crossref]

  • [57] Lopardo, T., Lo Iacono, N., Marinari, B., Giustizieri, M.L., Cyr, D.G., Merlo, G., Crosti, F., Costanzo, A. and Guerrini, L. Claudin-1 is a p63 target gene with a crucial role in epithelial development. PLoS One 3 (2008) e2715.

  • [58] Gressner, O., Schilling, T., Lorenz, K., Schulze Schleithoff, E., Koch, A., Schulze-Bergkamen, H., Lena, A.M., Candi, E., Terrinoni, A., Catani, M.V., Oren, M., Melino, G., Krammer, P.H., Stremmel, W. and Müller, M. TAp63alpha induces apoptosis by activating signaling via death receptors and mitochondria. EMBO J. 24 (2005) 2458–2471. [Crossref]

  • [59] Antonini, D., Dentice, M., Mahtani, P., De Rosa, L., Della Gatta, G., Mandinova, A., Salvatore, D., Stupka, E. and Missero, C. Tprg, a gene predominantly expressed in skin, is a direct target of the transcription factor p63. J. Invest. Dermatol. 128 (2008) 1676–1685. [Crossref]

  • [60] Koster, M.I., Dai, D., Marinari, B., Sano, Y., Costanzo, A., Karin, M. and Roop, D.R. p63 induces key target genes required for epidermal morphogenesis. Proc. Natl. Acad. Sci. USA 104 (2007) 3255–3260. [Crossref]

  • [61] Gu, X.L., Coates, P.J., Boldrup, L. and Nylander, K. p63 contributes to cell invasion and migration in squamous cell carcinoma of the head and neck. Cancer Lett. 263 (2008) 26–34. [Crossref]

  • [62] Ihrie, R.A., Marques, M.R., Nguyen, B.T., Horner, J.S., Papazoglu, C., Bronson, R.T., Mills, A.A. and Attardi, L.D. Perp is a p63-regulated gene essential for epithelial integrity. Cell 120 (2005) 843–856. [Crossref]

  • [63] Wu, G., Nomoto, S., Hoque, M.O., Dracheva, T., Osada, M., Lee, C.C., Dong, S.M., Guo, Z., Benoit, N., Cohen, Y., Rechthand, P., Califano, J., Moon, C.S., Ratovitski, E., Jen, J., Sidransky, D. and Trink, B. DeltaNp63alpha and TAp63alpha regulate transcription of genes with distinct biological functions in cancer and development. Cancer Res. 63 (2003) 2351–2357.

  • [64] Boldrup, L., Coates, P.J., Gu, X. and Nylander, K. DeltaNp63 isoforms differentially regulate gene expression in squamous cell carcinoma: identification of Cox-2 as a novel p63 target. J. Pathol. 218 (2009) 428–436.

  • [65] Osada, M., Ohba, M., Kawahara, C., Ishioka, C., Kanamaru, R., Katoh, I., Ikawa, Y., Nimura, Y., Nakagawara, A., Obinata, M. and Ikawa, S. Cloning and functional analysis of human p51, which structurally and functionally resembles p53. Nat. Med. 4 (1998) 839–843. [Crossref]

  • [66] Sunahara, M., Shishikura, T., Takahashi, M., Todo, S., Yamamoto, N., Kimura, H., Kato, S., Ishioka, C., Ikawa, S., Ikawa, Y. and Nakagawara, A. Mutational analysis of p51A/TAp63gamma, a p53 homolog, in non-small cell lung cancer and breast cancer. Oncogene 18 (1999) 3761–3765.

  • [67] Hibi, K., Trink, B., Patturajan, M., Westra, W.H., Caballero, O.L., Hill, D.E., Ratovitski, E.A., Jen, J. and Sidransky, D. AIS is an oncogene amplified in squamous cell carcinoma. Proc. Natl. Sci. USA 97 (2000) 5462–5467. [Crossref]

  • [68] Flores, E.R., Sengupta, S., Miller, J.B., Newman, J.J., Bronson, R., Crowley, D., Yang, A., McKeon, F. and Jacks, T. Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell 7 (2005) 363–373. [Crossref]

  • [69] Keyes, W.M., Vogel, H., Koster, M.I., Guo, X.C., Qi, Y., Petherbridge, K.M., Roop, D.R., Bradley, A. and Mills, A.A. p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors. Proc. Natl. Acad. Sci. USA 103 (2006) 8435–8440. [Crossref]

  • [70] Keyes, W.M., Wu, Y., Vogel, H., Guo, X.C., Lowe, S.W. and Mills, A.A. p63 deficiency activates a program of cellular senescence and leads to accelerated aging. Genes Dev. 19 (2005) 1986–1999. [Crossref]

  • [71] Djelloul, S., Tarunina, M., Barnouin, K., Mackay, A. and Jat, P.S. Differential protein expression, DNA binding and interaction with SV40 large tumour antigen implicate the p63-family of proteins in replicative senescence. Oncogene 21 (2002) 981–989. [Crossref]

  • [72] Guo, X.C., Keyes, W.M., Papazoglu, C., Zuber, J., Li, W.Z., Lowe, S.W., Vogel, H. and Mills, A.A. TAp63 induces senescence and suppresses tumorigenesis in vivo. Nature Cell Biol. 11 (2009) 1451–1457. [Crossref]

  • [73] Koster, M.I., Lu, S.L., White, L.D., Wang, X.J. and Roop, D.R. Reactivation of developmentally expressed p63 isoforms predisposes to tumor development and progression. Cancer Res. 66 (2006) 3981–3986. [Crossref]

  • [74] Koster, M.I., Kim, S., Mills, A.A., DeMayo, F.J. and Roop, D.R. p63 is the molecular switch for initiation of an epithelial stratification program. Gen. Dev. 18 (2004) 126–131. [Crossref]

  • [75] Mundt, H.M., Stremmel, W., Melino, G., Krammer, P.H., Schilling, T. and Müller, M. Dominant negative (DeltaN) p63alpha induces drug resistance in hepatocellular carcinoma by interference with apoptosis signaling pathways. Biochem. Biophys. Res. Commun. 396 (2010) 335–341.

  • [76] Nylander, K., Coates, P.J. and Hall, P.A. Characterization of the expression pattern of p63 alpha and delta Np63 alpha in benign and malignant oral epithelial lesions. Int. J. Cancer. 87 (2000) 368–372. [Crossref]

  • [77] Crook, T., Nicholls, J.M., Brooks, L., O’Nions, J. and Allday, M.J. High level expression of deltaNp63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)? Oncogene 19 (2000) 3439–3444. [Crossref]

  • [78] Tonon, G., Brennan, C., Protopopov, A., Maulik, G., Feng, B., Zhang, Y., Khatry, D.B., You, M.J., Aguirre, A.J., Martin, E.S., Yang, Z., Ji, H., CHin, L., Wong, K.K. and Depinho, R.A. Common and contrasting genomic profiles among the major human lung cancer subtypes. Cold Spring Harb. Symp. Quant. Biol. 70 (2005) 11–24. [Crossref]

  • [79] Davison, T.S., Vagner, C., Kaghad, M., Ayed, A., Caput, D. and Arrowsmith, C.H. p73 and p63 are homotetramers capable of weak heterotypic interactions with each other but not with p53. J. Biol. Chem. 274 (1999) 18709–18714. [Crossref]

  • [80] Gaiddon, C., Lokshin, M., Ahn, J., Zhang T., and Prives, C. A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain. Mol. Cell. Biol. 21 (2001) 1874–1887. [Crossref]

  • [81] Strano, S., Fontemaggi, G., Costanzo, A., Rizzo, M.G., Monti, O., Baccarini, A., Del Sal, G., Levrero, M., Sacchi, A., Oren, M. and Blandino, G. Physical interaction with human tumor-derived p53 mutants inhibits p63 activities. J. Biol. Chem. 277 (2002) 18817–18826.

  • [82] Yang, A., Zhu, Z., Kapranov, P., McKeon, F., Church, G.M., Gingeras, T.R. and Struhl, K. Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells. Mol. Cell 24 (2006) 593–602. [Crossref]

  • [83] Romano, R.A., Birkaya, B. and Sinha, S. Defining the regulatory elements in the proximal promoter of Delta Np63 in keratinocytes: Potential roles for Sp1/Sp3, NF-Y, and p63. J. Invest. Dermatol. 126 (2006) 1469–1479. [Crossref]

  • [84] Li, N., Li, H., Cherukuri, P., Farzan, S., Harmes, D.C. and DiRenzo, J. TA-p63-gamma regulates expression of Delta N-p63 in a manner that is sensitive to p53. Oncogene 25 (2006) 2349–2359. [Crossref]

  • [85] Lefkimmiatis, K., Caratozzolo, M.F., Merlo, P., D’Erchia, A.M., Navarro, B., Levrero, M., Sbisa, E. and Tullo, A. p73 and p63 sustain cellular growth by transcriptional activation of cell cycle progression genes. Cancer Res. 69 (2009) 8563–8571. [Crossref]

  • [86] Leong, C.O., Vidnovic, N., DeYoung, M.P., Sgroi, D. and Ellisen, L.W. The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers. J. Clin. Invest. 117 (2007) 1370–1380. [Crossref]

  • [87] Silver, D.P., Richardson, A.L., Eklund, A.C., Wang, Z.C., Szallasi, Z., Li, Q., Juul, N., Leong, C.O., Calogrias, D., Buraimoh, A., Fatima, A., Gelman, R.S., Ryan, P.D., Tung, N.M., De Nicolo, A., Ganesan, S., Miron, A., Colin, C., Sgroi, D.C., Ellisen, L.W., Winer, E.P. and Garber, J.E. Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J. Clin. Oncol. 28 (2010) 1145–1153. [Crossref]

  • [88] Rocco, J.W., Leong, C.O., Kuperwasser, N., DeYoung, M.P. and Ellisen, L.W. p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis. Cancer Cell 9 (2006) 45–56. [Crossref]

  • [89] Thurfjell, N., Coates, P.J., Vojtesek, B., Benham-Motlagh, P., Eisold, M. and Nylander, K. Endogenous p63 acts as a survival factor for tumour cells of SCCHN origin. Int. J. Mol. Med. 16 (2005) 1065–1070.

  • [90] Barbieri, C.E., Tang, L.J., Brown, K.A. and Pietenpol, J.A.. Loss of p63 leads to increased cell migration and up-regulation of genes involved in invasion and metastasis. Cancer Res. 66 (2006) 7589–7597. [Crossref]

  • [91] Adorno, M., Cordenonsi, M., Montagner, M., Dupont, S., Wong, C., Hann, B., Solari, A., Bobisse, S., Rondina, M.B., Guzzardo, V., Parenti, A.R., Rosato, A., Bicciato, S., Balmain, A. and Piccolo, S. A mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis. Cell 137 (2009) 87–98. [Crossref]

  • [92] Carroll, D.K., Carroll, J.S., Leong, C.O., Cheng, F., Brown, M., Mills, A.A., Brugge, J.S. and Ellisen, L.W. p63 regulates an adhesion programme and cell survival in epithelial cells. Nature Cell Biol. 8 (2006) 551–561. [Crossref]

  • [93] Su, X., Chakravarti, D., Cho, M.S., Liu, L., Gi, Y.J., Lin, Y.L., Leung, M.L., El-Naggar, A., Creighton, C.J., Suraokar, M.B., Wistuba, I. and Flores, E.R. TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature 467 (2010) 986–990.

  • [94] Bamberger, C., Hafner, A., Schmale, H. and Werner, S. Expression of different p63 variants in healing skin wounds suggests a role of p63 in reepithelialization and muscle repair. Wound Repair Regen. 13 (2005) 41–50. [Crossref]

  • [95] Thurfjell, N., Coates, P.J., Wahlin, Y.B., Arvidsson, E. and Nylander, K. Downregulation of TAp63 and unaffected levels of p63beta distinguishes oral wounds from SCCHN. Cell Cycle 5 (2006) 555–557. [Crossref]

  • [96] Ma, D.K, Bonaguidi, M.A., Ming, G.L. and Song, H. Adult neural stem cells in the mammalian central nervous system. Cell. Res. 19 (2009) 672–682. [Crossref]

  • [97] Gibelli, B., El-Fattah, A, Giugliano, G., Proh, M. and Grosso, E. Thyroid stem cells — danger or resource? Acta Otorhinolaryngol. Ital. 29 (2009) 290–295.

  • [98] Wu, X., Wang, S., Chen, B. and An, X. Muscle-derived stem cells: isolation, characterization, differentiation, and application in cell and gene therapy. Cell Tissue Res. 340 (2010) 549–567.

  • [99] Snyder, J.C, Teisanu, R.M. and Stripp, B.R. Endogenous lung stem cells and contribution to disease. J. Pathol. 217 (2009) 254–264.

  • [100] Little, M.H. and Bertram, J.F. Is there such a thing as a renal stem cell? J. Am. Soc. Nephrol. 20 (2009) 2112–2117. [Crossref]

  • [101] Pincelli, C. and Marconi, A. Keratinocyte stem cells: friends and foes. J. Cell. Physiol. 225 (2010) 310–315. [Crossref]

  • [102] Katsumoto, K., Shiraki, N., Miki, R. and Kume, S. Embryonic and adult stem cell systems in mammals: ontology and regulation. Dev. Growth. Differ. 52 (2010) 115–129. [Crossref]

  • [103] Petersen, O.W. and Polyak, K. Stem cells in the human breast. Cold Spring Harb. Perspect. Biol. 2 (2010) a003160.

  • [104] Ratajczak, M.Z., Zuba-Surma, E.K., Machalinski, B. and Kucia, M. Bonemarrow-derived stem cells — our key to longevity? J. Appl. Genet. 48 (2007) 307–319. [Crossref]

  • [105] Beltrami, A.P., Barlucchi, L., Torella, D., Baker, M., Limana, F., Chimenti, S., Kasahara, H., Rota, M., Musso, E., Urbanek, K., Leri, A., Kajstura, J., Nadal-Ginard, B. and Anversa, P. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114 (2003) 763–776. [Crossref]

  • [106] Tumbar, T., Guasch, G., Greco, V., Blanpain, C., Lowry, W.E., Rendl, M. and Fuchs, E. Defining the epithelial stem cell niche in skin. Science 303 (2004) 359–363.

  • [107] Collins, C.A. and Partridge, T.A. Self-renewal of the adult skeletal muscle satellite cell. Cell Cycle 4 (2005) 1338–1341. [Crossref]

  • [108] Herrera, M.B., Bruno, S., Buttiglieri, S., Tetta, C., Gatti, S., Deregibus, M.C., Bussolati, B. and Camussi, G. Isolation and characterization of a stem cell population from adult human liver. Stem Cells 24 (2006) 2840–2850. [Crossref]

  • [109] Yang, A., Schweitzer, R., Sun, D.Q., Kaghad, M., Walker, N., Bronson, R.T., Tabin, C., Sharpe, A., Caput, D., Crum, C. and McKeon, F. p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398 (1999) 714–718.

  • [110] Mills, A.A., Zheng, B.H., Wang, X.J., Vogel, H., Roop, D.R. and Bradley, A. p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398 (1999) 708–713.

  • [111] Pellegrini, G., Dellambra, E., Golisano, O., Martinelli, E., Fantozzi, I., Bondanza, S., Ponzin, D., McKeon, F. and De Luca, M. p63 identifies keratinocyte stem cells. Proc. Natl. Acad. Sci. USA. 98 (2001) 3156–3161. [Crossref]

  • [112] Barbieri, C.E. and Pietenpol, J.A. p63 and epithelial biology. Exp. Cell. Res. 312 (2006) 695–706. [Crossref]

  • [113] Dellavalle, R.P., Egbert, T.B., Marchbank, A., Su, L.J., Lee, L.A. and Walsh, P. CUSP/p63 expression in rat and human tissues. J. Dermat. Sci. 27 (2001) 82–87.

  • [114] Rizzo, S., Attard, G. and Hudson, D.L. Prostate epithelial stem cells. Cell. Prolif. 38 (2005) 363–374. [Crossref]

  • [115] Signoretti, S., Waltregny, D., Dilks, J., Isaac, B., Lin, D., Garraway, L., Yang, A., Montironi, R., McKeon, F. and Loda, M. p63 is a prostate basal cell marker and is required for prostate development. Am. J. Pathol. 157 (2000) 1769–1775. [Crossref]

  • [116] Signoretti, S., Pires, M.M., Lindauer, M., Horner, J.W., Grisanzio, C., Dhar, S., Majumder, P., McKeon, F., Kantoff, P.W., Sellers, W.R., Loda, M. p63 regulates commitment to the prostate cell lineage. Proc. Natl. Acad. Sci. USA 102 (2005) 11355–11360. [Crossref]

  • [117] Senoo, M., Pinto, F., Crum, C.P. and McKeon, F. p63 is essential for the proliferative potential of stem cells in stratified epithelia. Cell 129 (2007) 523–536. [Crossref]

  • [118] Laurikkala, J., Mikkola, M.L., James, M., Tummers, M., Mills, A.A. and Thesleff, I. p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation. Development 133 (2006) 1553–1563. [Crossref]

  • [119] Mumm, J.S. and Kopan, R. Notch signaling: From the outside in. Dev. Biol. 228 (2000) 151–165. [Crossref]

  • [120] Stylianou, S., Clarke, R.B. and Brennan, K. Aberrant activation of notch signaling in human breast cancer. Cancer Res. 66 (2006) 1517–1525. [Crossref]

  • [121] Massi, D., Tarantini, F., Franchi, A., Paglierani, M., Di Serio, C., Pellerito, S., Leoncini, G., Cirino, G., Geppetti, P. and Santucci, M. Evidence for differential expression of Notch receptors and their ligands in melanocytic nevi and cutaneous malignant melanoma. Mod. Pathol. 19 (2006) 246–254. [Crossref]

  • [122] Rose, S.L., Kunnimalaiyaan, M., Drenzek, J. and Seiler, N. Notch 1 signaling is active in ovarian cancer. Gynecol. Oncol. 117 (2010) 130–133. [Crossref]

  • [123] Grudzien, P., Lo, S., Albain, K.S., Robinson, P., Rajan, P., Strack, P.R., Golde, T.E., Miele, L. and Foreman, K.E. Inhibition of Notch signaling reduces the stem-like population of breast cancer cells and prevents mammosphere formation. Anticancer Res. 30 (2010) 3853–3867.

  • [124] Artavanis-Tsakonas, S., Rand, M.D. and Lake, R.J. Notch signaling: cell fate control and signal integration in development. Science 284 (1999) 770–776.

  • [125] Lowell, S., Jones, P., Le Roux, I., Dunne, J. and Watt, F.M. Stimulation of human epidermal differentiation by delta-notch signalling at the boundaries of stem-cell clusters. Curr. Biol. 10 (2000) 491–500. [Crossref]

  • [126] Rangarajan, A., Talora, C., Okuyama, R., Nicolas, M., Mammucari, C., Oh, H., Aster, J.C., Krishna, S., Metzger, D., Chambon, P., Miele, L., Aguet, M., Radtke, F. and Dotto, G.P. Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. EMBO J. 20 (2001) 3427–3436. [Crossref]

  • [127] Nickoloff, B.J., Qin, J.Z., Chaturvedi, V., Denning, M.F., Bonish, B. and Miele, L. Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocates through NF-kappaB and PPARgamma. Cell Death Differ. 9 (2002) 842–855. [Crossref]

  • [128] Talora, C., Sgroi, D.C., Crum, C.P. and Dotto, G.P. Specific downmodulation of Notch1 signaling in cervical cancer cells is required for sustained HPV-E6/E7 expression and late steps of malignant transformation. Genes Dev. 16 (2002) 2252–2263. [Crossref]

  • [129] Nicolas, M., Wolfer, A., Raj, K., Kummer, J.A., Mill, P., van Noort, M., Hui, C.C., Clevers, H., Dotto, G.P. and Radtke, F. Notch1 functions as a tumor suppressor in mouse skin. Nat. Genet. 33 (2003) 416–421. [Crossref]

  • [130] Okuyama, R., Ogawa, E., Nagoshi, H., Yabuki, M., Kurihara, A., Terui, T., Aiba, S., Obinata, M., Tagami, H. and Ikawa, S. p53 homologue, p51/p63, maintains the immaturity of keratinocyte stem cells by inhibiting Notch1 activity. Oncogene 26 (2007) 4478–4488. [Crossref]

  • [131] Nguyen, B.C., Lefort, K., Mandinova, A., Antonini, D., Devgan, V., Della Gatta, G., Koster, M.I., Zhang, Z., Wang, J., Tommasi di Vignano, A., Kitajewski, J., Chiorino, G., Roop, D.R., Missero, C. and Dotto, G.P. Crossregulation between Notch and p63 in keratinocyte commitment to differentiation. Genes Dev. 20 (2006) 1028–1042. [Crossref]

  • [132] Yugawa, T., Narisawa-Saito, M., Yoshimatsu, Y., Haga, K., Ohno, S., Egawa, N., Fujita, M. and Kiyono, T. ΔNp63α repression of the Notch1 gene supports the proliferative capacity of normal human keratinocytes and cervical cancer cells. Cancer Res. 70 (2010) 4034–4044. [Crossref]

  • [133] Ma, J., Meng, Y., Kwiatkowski, D.J., Chen, X., Peng, H., Sun, Q., Zha, X., Wang, F., Wang, Y., Jing, Y., Zhang, S., Chen, R., Wang, L., Wu, E., Cai, G., Malinowska-Kolodziej, I., Liao, Q., Liu, Y., Zhao, Y., Sun, Q., Xu, K., Dai, J., Han, J., Wu, L., Zhao, R.C., Shen, H. and Zhang, H. Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade. J. Clin. Invest. 120 (2010) 103–114.

  • [134] Yalcin-Ozuysal, O., Fiche, M., Guitierrez, M., Wagner, K.U., Raffoul, W. and Brisken, C. Antagonistic roles of Notch and p63 in controlling mammary epithelial cell fates. Cell Death Differ. 17 (2010) 1600–1612. [Crossref]

  • [135] Bienz, M. and Clevers, H. Linking colorectal cancer to Wnt signaling. Cell m103 (2000) 311–320. [Crossref]

  • [136] Logan, C.Y. and Nusse, R. The Wnt signaling pathway in development and disease. Annu. Rev. Cell. Dev. Biol. 20 (2004) 781–810. [Crossref]

  • [137] Kléber, M. and Sommer, L. Wnt signaling and the regulation of stem cell function. Curr. Opin. Cell. Biol. 16 (2004) 681–687. [Crossref]

  • [138] Reya, T. and Clevers, H. Wnt signalling in stem cells and cancer. Nature 434 (2005) 843–850.

  • [139] Gu, B., Watanabe, K. and Dai, X. Epithelial stem cells: an epigenetic and Wnt-centric perspective. J. Cell. Biochem. 110 (2010) 1279–1287. [Crossref]

  • [140] Drewelus, I., Göpfert, C., Hippel, C., Dickmanns, A., Damianitsch, K., Pieler, T. and Dobbelstein, M. p63 antagonizes Wnt-induced transcription. Cell Cycle 9 (2010) 580–587. [Crossref]

  • [141] Iseki, S., Araga, A., Ohuchi, H., Nohno, T., Yoshioka, H., Hayashi, F. and Noji, S. Sonic hedgehog is expressed in epithelial cells during development of whisker, hair, and tooth. Biochem. Biophys. Res. Commun. 218 (1996) 688–693. [Crossref]

  • [142] Ho, K.S. and Scott, M.P. Sonic hedgehog in the nervous system: functions, modifications and mechanisms. Curr. Opin. Neurobiol. 12 (2002) 57–63. [Crossref]

  • [143] Freestone, S.H., Marker, P., Grace, O.C., Tomlinson, D.C., Cunha, G.R., Harnden, P. and Thomson, A.A. Sonic hedgehog regulates prostatic growth and epithelial differentiation. Dev. Biol. 264 (2003) 352–362. [Crossref]

  • [144] Vezina, C.M. and Bushman, A.W. Hedgehog signaling in prostate growth and benign prostate hyperplasia. Curr. Urol. Rep. 8 (2007) 275–280. [Crossref]

  • [145] Ramalho-Santos, M., Melton, D.A. and McMahon, A.P. Hedgehog signals regulate multiple aspects of gastrointestinal development. Development 127 (2000) 2763–2772.

  • [146] Sicklick, J.K., Li, Y.X., Jayaraman, A., Kannangai, R., Qi, Y., Vivekanandan, P., Ludlow, J.W., Owzar, K., Chen, W., Torbenson, M.S. and Diehl, A.M. Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis. Carcinogenesis 27 (2006) 748–757.

  • [147] Yoshikawa, K., Shimada, M., Miyamoto, H., Higashijima, J., Miyatani, T., Nishioka, M., Kurita, N., Iwata, T. and Uehara, H. Sonic hedgehog relates to colorectal carcinogenesis. J. Gastroenterol. 44 (2009) 1113–1117. [Crossref]

  • [148] Dormoy, V., Danilin, S., Lindner, V., Thomas, L., Rothhut, S., Coquard, C., Helwig, J.J., Jacqmin, D., Lang, H. and Massfelder, T. The sonic hedgehog signaling pathway is reactivated in human renal cell carcinoma and plays orchestral role in tumor growth. Mol. Cancer 8 (2009) 123. [Crossref]

  • [149] Berman, D.M., Karhadkar, S.S., Hallahan, A.R., Pritchard, J.I., Eberhart, C.G., Watkins, D.N., Chen, J.K., Cooper, M.K., Taipale, J., Olson, J.M. and Beachy, P.A. Medulloblastoma growth inhibition by hedgehog pathway blockade. Science 297 (2002) 1559–1561.

  • [150] Kubo, M., Nakamura, M., Tasaki, A., Yamanaka, N., Nakashima, H., Nomura, M., Kuroki, S. and Katano, M. Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res. 64 (2004) 6071–6074. [Crossref]

  • [151] Chen, X., Horiuchi, A., Kikuchi, N., Osada, R., Yoshida, J., Shiozawa, T. and Konishi, I. Hedgehog signal pathway is activated in ovarian carcinomas, correlating with cell proliferation: it’s inhibition leads to growth suppression and apoptosis. Cancer Sci. 98 (2007) 68–76. [Crossref]

  • [152] Sheng, T., Li, C., Zhang, X., Chi, S., He, N., Chen, K., McCormick, F., Gatalica, Z. and Xie, J. Activation of the hedgehog pathway in advanced prostate cancer. Mol. Cancer 3 (2004) 29. [Crossref]

  • [153] Caserta, T.M., Kommagani, R., Yuan, Z.A., Robbins, D.J., Merce, r C.A. and Kadakia, M.P. p63 overexpression induces the expression of sonic hedgehog. Mol. Cancer Res. 4 (2006) 759–768. [Crossref]

  • [154] Hatsell, S.J. and Cowin, P. Gli3-mediated repression of Hedgehog targets is required for normal mammary development. Development 133 (2006) 3661–3670. [Crossref]

  • [155] Liu, S., Dontu, G., Mantle, I.D., Patel, S., Ahn, N.S., Jackson, K.W., Suri, P. and Wicha, M.S. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 66 (2006) 6063–6071. [Crossref]

  • [156] Kubo, M., Nakamura, M., Tasaki, A., Yamanaka, N., Nakashima, H., Nomura, M., Kuroki, S. and Katano, M. Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res. 64 (2004) 6071–6074. [Crossref]

  • [157] Li, N., Singh, S., Cherukuri, P., Li, H., Yuan, Z., Ellisen, L.W., Wang, B., Robbins, D., DiRenzo, J. Reciprocal intraepithelial interactions between TP63 and hedgehog signaling regulate quiescence and activation of progenitor elaboration by mammary stem cells. Stem Cells 26 (2008) 1253–1264. [Crossref]

  • [158] Boominathan, L. The guardians of the genome (p53, TA-p73, and TA-p63) are regulators of tumor suppressor miRNAs network. Cancer Metastasis Rev. 29 (2010) 613–639. [Crossref]

  • [159] Davidson, M.R., Larsen, J.E., Yang, I.A., Hayward, N.K., Clarke, B.E., Duhig, E.E., Passmore, L.H., Bowman, R.V. and Fong, K.M. MicroRNA-218 is deleted and downregulated in lung squamous cell carcinoma. PLoS One 5 (2010) e12560.

  • [160] Melo, S.A. and Esteller, M. Dysregulation of microRNAs in cancer: Playing with fire. FEBS Lett. (2010) Epub ahead of print.

  • [161] Grelier, G., Voirin, N., Ay, A.S., Cox, D.G., Chabaud, S., Treilleux, I., Léon-Goddard, S., Rimokh, R., Mikaelian, I., Venoux, C., Puisieux, A., Lasset, C. and Moyret-Lalle, C. Prognostic value of Dicer expression in human breast cancer and association with the mesenchymal phenotype. Br. J. Cancer. 101 (2009) 673–683. [Crossref]

  • [162] Wang, Y., Medvid, R., Melton, C., Jaenisch, R. and Blelloch, R. DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat. Genet. 39 (2007) 380–385. [Crossref]

  • [163] Cui, X.S., Shen, X.H. and Kim, N.H. Dicer1 expression in preimplantation mouse embryos: Involvement of Oct3/4 transcription at the blastocyst stage. Biochem. Biophys. Res. Commun. 352 (2007) 231–236.

  • [164] Yi, R., Poy, M.N., Stoffel, M. and Fuchs, E. A skin microRNA promotes differentiation by repressing “stemness”. Nature 452 (2008) 225–229.

  • [165] Scheel, A.H., Beyer, U., Agami, R. and Dobbelstein, M. Immunofluorescence-based screening identifies germ cell associated microRNA 302 as an antagonist to p63 expression. Cell Cycle 8 (2009) 1426–1432. [Crossref]

  • [166] Lena, A.M., Shalom-Feuerstein, R., Rivetti di Val Cervo, P., Aberdam, D., Knight, R.A., Melino, G. and Candi, E. miR-203 represses “stemness” by repressing DeltaNp63. Cell Death Differ. 15 (2008) 1187–1195. [Crossref]

  • [167] Papagiannakopoulos, T., Shapiro, A. and Kosik, K.S. MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res. 68 (2008) 8164–8172. [Crossref]

  • [168] Manni, I., Artuso, S., Careccia, S., Rizzo, M.G., Baserga, R., Piaggio, G. and Sacchi, A. The microRNA miR-92 increases proliferation of myeloid cells and by targeting p63 modulates the abundance of its isoforms. FASEB J. 23 (2009) 3957–3966. [Crossref]

  • [169] Chan, J.A., Krichevsky, A.M. and Kosik, K.S. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 65 (2005) 6029–6033. [Crossref]

  • [170] Si, M.L., Zhu, S., Wu, H., Lu, Z., Wu, F. and Mo, Y.Y. miR-21-mediated tumor growth. Oncogene 26 (2007) 2799–2803. [Crossref]

  • [171] Meng, F., Henson, R., Lang, M., Wehbe, H., Maheshwari, S., Mendell, J.T., Jiang, J., Schmittgen, T.D. and Patel, T. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology 130 (2006) 2113–2129. [Crossref]

  • [172] Craig, A.L., Holcakova, J., Finlan, L.E., Nekulova, M., Hrstka, R., Gueven, N., DiRenzo, J., Smith, G., Hupp, T.R. and Vojtesek, B. DeltaNp63 transcriptionally regulates ATM to control p53 Serine-15 phosphorylation. Mol. Cancer 9 (2010) 195. [Crossref]

  • [173] Reya, T., Morrison, S.J., Clarke, M.F. and Weissman, I.L. Stem cells, cancer, and cancer stem cells. Nature 414 (2001) 105–111.

  • [174] Tan, B.T., Park, C.Y., Ailles, L.E. and Weissman, I.L. The cancer stem cell hypothesis: a work in progress. Lab. Invest. 86 (2006) 1203–1207. [Crossref]

  • [175] Schatton, T., Frank, N.Y. and Frank, M.H. Identification and targeting of cancer stem cells. Bioessays 31 (2009) 1038–1049. [Crossref]

  • [176] Al-Hajj, M., Wicha, M.S., Benito-Hernandez, A., Morrison, S.J. and Clarke, M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 100 (2003) 3983–3988.

  • [177] Prince, M.E., Sivanandan, R., Kaczorowski, A., Wolf, G.T., Kaplan, M.J., Dalerba, P., Weissman, I.L., Clarke, M.F. and Ailles, L.E. Identification of a subpopulation of cells with cancer stem cells properties in head and neck squamous cell carcinoma. Proc. Natl. Acad. Sci. USA 104 (2007) 973–978. [Crossref]

  • [178] Boldrup, L., Coates, P.J., Gu, X. and Nylander, K. DeltaNp63 isoforms regulate CD44 and keratins 4, 6, 14 and 19 in squamous cell carcinoma of head and neck. J. Pathol. 213 (2007) 384–391.

  • [179] Du, Z., Li, J., Wang, L., Bian, C., Wang, Q., Liao, L., Dou, X., Bian, X. and Zhao, R.C. Overexpression of ΔNp63α induces a stem cell phenotype in MCF7 breast carcinoma cell line through the Notch pathway. Cancer Sci. 101 (2010) 2417–2424. [Crossref]

About the article

Published Online: 2011-03-26

Published in Print: 2011-06-01

Citation Information: Cellular and Molecular Biology Letters, ISSN (Online) 1689-1392, DOI: https://doi.org/10.2478/s11658-011-0009-9. Export Citation

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Alan F. Brown, Deepika Sirohi, Junya Fukuoka, Philip T. Cagle, Maria Policarpio-Nicolas, David Tacha, and Jaishree Jagirdar
Archives of Pathology & Laboratory Medicine, 2013, Volume 137, Number 9, Page 1274
Marta Nekulova, Jitka Holcakova, Rudolf Nenutil, Rembert Stratmann, Pavla Bouchalova, Petr Müller, Lucie Mouková, Philip J. Coates, and Borivoj Vojtesek
Virchows Archiv, 2013, Volume 463, Number 3, Page 415
ZhongFa Zhang, Sharmistha Pal, Yingtao Bi, Julia Tchou, and Ramana V Davuluri
Genome Medicine, 2013, Volume 5, Number 4, Page 33
Maisam Makarem, Benjamin T. Spike, Christopher Dravis, Nagarajan Kannan, Geoffrey M. Wahl, and Connie J. Eaves
Journal of Mammary Gland Biology and Neoplasia, 2013, Volume 18, Number 2, Page 209
Qin Huang, Hongyan Wu, Ling Nie, Jiong Shi, Abraham Lebenthal, Jieyu Chen, Qi Sun, Jun Yang, Lily Huang, and Qing Ye
The American Journal of Surgical Pathology, 2013, Volume 37, Number 4, Page 467
Xu-Yong Lin, Yang Liu, Yong Zhang, Juan-Han Yu, and En-Hua Wang
Diagnostic Pathology, 2012, Volume 7, Number 1, Page 118
Varun V Prabhu, Joshua E Allen, Bo Hong, Shengliang Zhang, Hairong Cheng, and Wafik S El-Deiry
Expert Opinion on Therapeutic Targets, 2012, Volume 16, Number 12, Page 1161
G. Vasmatzis, S. H. Johnson, R. A. Knudson, R. P. Ketterling, E. Braggio, R. Fonseca, D. S. Viswanatha, M. E. Law, N. S. Kip, N. Ozsan, S. K. Grebe, L. A. Frederick, B. W. Eckloff, E. A. Thompson, M. E. Kadin, D. Milosevic, J. C. Porcher, Y. W. Asmann, D. I. Smith, I. V. Kovtun, S. M. Ansell, A. Dogan, and A. L. Feldman
Blood, 2012, Volume 120, Number 11, Page 2280
Qin Huang, Jiong Shi, Qi Sun, Xiangshan Fan, Anning Feng, Hongyan Wu, Qiang Zhou, Chenggong Yu, Hiroshi Mashimo, and Gregory Y. Lauwers
Human Pathology, 2012, Volume 43, Number 12, Page 2138
Xiaorong Li, Jing Chen, Yong Yi, Chenghua Li, and Yujun Zhang
Biochemical and Biophysical Research Communications, 2012, Volume 423, Number 2, Page 338
Michael E. Kallen, Melinda E. Sanders, Adriana L. Gonzalez, Jennifer O. Black, Vicki L. Keedy, Kenneth R. Hande, Kelly C. Homlar, Jennifer L. Halpern, Ginger E. Holt, Herbert S. Schwartz, Cheryl M. Coffin, and Justin M. M. Cates
Tumor Biology, 2012, Volume 33, Number 5, Page 1639
Daisuke Nonaka
The American Journal of Surgical Pathology, 2012, Volume 36, Number 6, Page 895
Eviatar Natan and Andreas C. Joerger
Journal of Molecular Biology, 2012, Volume 415, Number 3, Page 503
Michael E. Kallen, Flavia G. Nunes Rosado, Adriana L. Gonzalez, Melinda E. Sanders, and Justin M. M. Cates
Pathology & Oncology Research, 2012, Volume 18, Number 1, Page 97
G Melino
Cell Death and Differentiation, 2011, Volume 18, Number 9, Page 1487

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