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

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, prese...

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Veröffentlicht in:Biological chemistry 2012-05, Vol.393 (5), p.413-420
Hauptverfasser: Chung, Hyunjae, Hamza, Magda, Oikonomopoulou, Katerina, Gratio, Valérie, Saifeddine, Mahmoud, Virca, G. Duke, Diamandis, Eleftherios P., Hollenberg, Morley D., Darmoul, Dalila
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Sprache:eng
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Zusammenfassung: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.
ISSN:1431-6730
1437-4315
DOI:10.1515/bc-2011-231