Increased Src activity disrupts cadherin/catenin-mediated homotypic adhesion in human colon cancer and transformed rodent cells

Rosalyn Irby, Timothy J. Yeatman

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

Src has been implicated in the development and progression of human colon cancer. Because the capacity for tumor cells to dissociate from the primary tumor is a critical step in the development of metastases, the effect of a naturally occurring, activated Src-531 on intercellular adhesion was examined. Homotypic adhesion was assessed using dissociation assays on Src-transformed rat fibroblasts and human colon cancer cell lines. The data indicate that both rodent and human cells expressing the mutant Src protein display up to 7-fold less homotypic adhesion than do wild-type cells (P < 0.01). Experiments demonstrated that cadherin was phosphorylated in cells transfected with activated Src and that cadherin/catenin complexes were disrupted as a result. Experiments using dominant negative (DN) Src or an Src-specific inhibitor (PD 180970), demonstrated that adhesion was restored when Src activity was inhibited in Src-531 transfectants, confirming that Src is a causal factor in the decreased homotypic adhesion observed. In addition, DN Ras, DN focal adhesion kinase (FAK), but not Stat3β, restored intercellular adhesion, which suggested that Ras and FAK may be downstream effectors of Src-mediated homotypic adhesion. Collectively, these data support a role for Src, Ras, and FAK in the regulation of intercellular adhesion, which may in turn regulate metastatic potential of human colon cancer cells.

Original languageEnglish (US)
Pages (from-to)2669-2674
Number of pages6
JournalCancer Research
Volume62
Issue number9
StatePublished - May 1 2002

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Increased Src activity disrupts cadherin/catenin-mediated homotypic adhesion in human colon cancer and transformed rodent cells'. Together they form a unique fingerprint.

  • Cite this