Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells

Rebecca S. Henkhaus, Eugene W. Gerner, Natalia A. Ignatenko

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Kallikrein 6 (KLK6) is a trypsin-like serine peptidase whose relevance in various types of cancers is currently being explored. Previous studies have shown that KLK6 mRNA is upregulated in colon and gastric cancers; however, the regulatory mechanisms and phenotypic consequences of this upregulation are largely unknown. Activating K-RAS mutations are common in colon cancer, occurring in approximately 50% of cases. We have recently reported the upregulation of KLK6 mRNA in Caco2 human colon cancer cells stably transfected with a mutant K-RAS allele (K-RASG12V). In this study we examined the pattern of K-RAS-dependent KLK6 expression and secretion in colon cancer cells. Using pharmacological inhibitors of pathways downstream of K-RAS, we could show that the PI3K and p42/44 MAPK pathways play an important role in the induction of KLK6 in mutant K-RAS-expressing colon cancer cells. Increased KLK6 expression enhanced colon cancer cell migration through laminin and Matrigel. Inhibition of KLK6 using small interference RNA treatment or a specific KLK6 antibody in Caco2 cells stably expressing the mutant K-RAS and in SW480 cells carrying a mutation in the K-RAS oncogene resulted in a reduction in invasiveness through cell culture inserts. These data support the oncogenic role of KLK6 in colorectal cancer.

Original languageEnglish (US)
Pages (from-to)757-764
Number of pages8
JournalBiological Chemistry
Volume389
Issue number6
DOIs
StatePublished - Jun 1 2008

Keywords

  • Cell migration
  • Colon cancer
  • K-Ras oncogene
  • Kallikrein 6
  • Matrigel invasion

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

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