title: Kallikrein-related peptidase signaling in colon carcinoma cells: targeting proteinase-activated receptors.
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.
authors.affiliation: Department of Physiology and Pharmacology, University of Calgary, AB, Canada.
authors.forename: Hyunjae
authors.initials: H
authors.lastname: Chung
authors.forename: Magda
authors.initials: M
authors.lastname: Hamza
authors.forename: Katerina
authors.initials: K
authors.lastname: Oikonomopoulou
authors.forename: Valérie
authors.initials: V
authors.lastname: Gratio
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Saifeddine
authors.forename: G Duke
authors.initials: GD
authors.lastname: Virca
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.forename: Morley D
authors.initials: MD
authors.lastname: Hollenberg
authors.forename: Dalila
authors.initials: D
authors.lastname: Darmoul
mesh_terms: D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D012333:RNA, Messenger; D044464:Receptor, PAR-2; C425336:KLK14 protein, human; D007610:Kallikreins