Increases in c-Yes expression level and activity promote motility but not proliferation of human colorectal carcinoma cells

Neoplasia. 2007 Sep;9(9):745-54. doi: 10.1593/neo.07442.

Abstract

Increases in the levels and/or activity of nonreceptor tyrosine kinases c-Src and c-Yes are often associated with colorectal carcinogenesis. The physiological consequences of increased c-Yes activity during the early and late stages of tumorigenesis, in addition to the degree of redundancy between c-Yes and c-Src in colorectal cancer cells, remain elusive. To study the consequences of increases in c-Yes levels and activity in later stages of colorectal carcinogenesis, we developed human colorectal cancer cell lines in which c-Yes levels and activity can be inducibly increased by a tightly controlled expression of wild-type c-Yes or by constitutively active mutants of c-Yes, c-YesY537F, and c-Yes Delta t6aa. c-Yes induction resulted in increased cell motility but did not promote proliferation either in vitro or in vivo. These results suggest that in later stages of colorectal carcinogenesis, elevations in c-Yes levels/activity may promote cancer spread and metastasis rather than tumor growth.

Keywords: c-Src; c-Yes; colon cancer; motility; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Cell Adhesion / physiology
  • Cell Division / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Doxycycline / pharmacology
  • Enzyme Induction / drug effects
  • Female
  • Humans
  • Mice
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-yes / genetics
  • Proto-Oncogene Proteins c-yes / physiology*
  • Recombinant Fusion Proteins / physiology
  • src-Family Kinases / physiology

Substances

  • Neoplasm Proteins
  • Recombinant Fusion Proteins
  • Proto-Oncogene Proteins c-yes
  • YES1 protein, human
  • src-Family Kinases
  • Doxycycline