Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells
- Resource Type
- research-article
- Authors
- Henkhaus, Rebecca S.; Gerner, Eugene W.; Ignatenko, Natalia A.
- Source
- Biological Chemistry. 389(6):757-764
- Subject
- cell migration
colon cancer
kallikrein 6
K-Ras oncogene
Matrigel invasion
Highlight: Kallikrein, kinins and kallikrein-related peptidases
- Language
- English
- ISSN
- 1437-4315
1431-6730
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.