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

Biol Chem. 2012 Apr;393(5):413-20. doi: 10.1515/bc-2011-231.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic
  • HT29 Cells
  • Humans
  • Kallikreins / genetics
  • Kallikreins / metabolism*
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, PAR-2 / metabolism*
  • Signal Transduction*


  • RNA, Messenger
  • Receptor, PAR-2
  • KLK14 protein, human
  • Kallikreins