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Publication Date:
May 2012
ISSN:
1437-4315
DOI:
10.1515/bc-2011-231

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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Ludwig, Stephan / Sies, Helmut / Stoffel, Markus / Turk, Boris / Wittinghofer, Alfred / Baumeister, Wolfgang / Bergeron, John / Bogyo, Matthew / Bürkle, Alexander / Cadenas, Enrique / Chiti, Fabrizio / Dikic, Ivan / Dobson, Christopher / Driessen, Arnold / Fritz, Hans / Gevaert, Kris / Hammann, Christian / Hartl, F. Ulrich / Häussinger, Dieter / Hiscott, John / Igarashi, Yasuyuki / Klotz, Lars-Oliver / Krüger, Achim / Magdolen, Viktor / Müschen, Markus / Narumiya, Shuh / Naumann, Michael / Pejler, Gunnar / Pfanner, Nikolaus / Pike, Robert / Potempa, Jan / Saftig, Paul / Sandhoff, Konrad / Schaffner, Walter / Sinning, Irmgard / Sommerhoff, Christian P.

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Kallikrein-related peptidase signaling in colon carcinoma cells: targeting proteinase-activated receptors

Hyunjae Chung1 / Magda Hamza2 / Katerina Oikonomopoulou1, 3, 4 / Valérie Gratio2 / Mahmoud Saifeddine1 / G. Duke Virca5 / Eleftherios P. Diamandis3 / Morley D. Hollenberg1 / 2

1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, T2N 1N4, Canada

2Institut National de la Santé et de la Recherche Médicale (INSERM) U773, Centre de Recherche Biomédicale Bichat-Beaujon, 75018 Paris, France

3Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, M5G 1X5, ON, Canada

4Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA

5Inflammation Research, Amgen Inc., Seattle, WA 98119, USA

Corresponding author

Citation Information: . Volume 393, Issue 5, Pages 413–420, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/bc-2011-231, May 2012

Publication History:
Received:
2011-10-18
Accepted:
2011-12-05

Abstract

We hypothesized that kallikrein-related peptidase 14 (KLK14) is produced by colonic tumors and can promote tumorigenesis by activating proteinase-activated receptors (PARs). We found that KLK14 is expressed in human colon adenocarcinoma cells but not in adjacent cancer-free tissue; KLK14 mRNA, present in colon cancer, leads to KLK14 protein expression and secretion; and KLK14 signals viaPAR-2 in HT-29 cells to cause (1) receptor activation/internalization, (2) increases in intracellular calcium, (3) stimulation of ERK1/2/MAP kinase phosphorylation, and (4) cell proliferation. We suggest that KLK14, acting via PAR-2, represents an autocrine/paracrine regulator of colon tumorigenesis.

Keywords: cancer; colon; kallikrein; PARs; proliferation; signaling

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