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Licensed Unlicensed Requires Authentication Published by De Gruyter September 22, 2017

Artemin promotes oncogenicity, metastasis and drug resistance in cancer cells

  • Kamal Hezam , Jiahao Jiang , Fumou Sun , Xinrong Zhang and Juan Zhang EMAIL logo


Artemin (ARTN) is a member of glial cell line-derived neurotrophic factor (GDNF) family of ligands, and its signaling is mediated via a multi-component receptor complex including the glycosylphosphatidylinositol-anchored GDNF family receptors a (GFRa1, GFRa3) and RET receptor tyrosine kinase. The major mechanism of ARTN action is via binding to a non-signaling co-receptor. The major function of ARTN is to drive the molecule to induce migration and axonal projection from sympathetic neurons. It also promotes the survival, proliferation and neurite outgrowth of sympathetic neurons in vitro. ARTN triggers oncogenicity and metastasis by the activation of the AKT signaling pathway. Recent studies have reported that the expression of ARTN in hepatocellular carcinoma is associated with increased tumor size, quick relapse and shorter survival. Furthermore, ARTN promotes drug resistance such as antiestrogens, doxorubicin, fulvestrant, paclitaxel, tamoxifen and trastuzumab. Moreover, ARTN also stimulates the radio-therapeutic resistance. This review highlights the proposed roles of ARTN in cancer cells and discusses recent results supporting its emerging role as an oncogenic, metastatic and drug-resisting agent with a special focus on how these new insights may facilitate rational development of ARTN for targeted therapies in the future.


We thank Dr. Ghulam Jilany Khan and Dr. Abdul Baset Abbas for critical reading of the manuscript. The authors’ research is supported by Natural Science Foundation of Jiangsu Province (BK20161459) and Jiangsu Province Qinglan Project (2014) – a project funded by the Priority Academic Program Development Innovation Program of Jiangsu Higher Education Institutions.

  1. Conflict of interest statement: The authors have no conflict of interest to declare.


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Received: 2017-04-22
Accepted: 2017-06-02
Published Online: 2017-09-22
Published in Print: 2017-12-20

©2018 Walter de Gruyter GmbH, Berlin/Boston

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