Specific oncogenic activity of the Src-family tyrosine kinase c-Yes in colon carcinoma cells

Florence Sancier1, Aurélie Dumont, Audrey Sirvent

  • 1Institut de Recherches Servier, Croissy-sur-Seine, France.

Plos One
|March 11, 2011
PubMed

Insights

c-Yes, a Src tyrosine kinase family member, drives colon cancer progression by regulating cell adhesion and metastasis. Silencing c-Yes inhibits tumor growth and spread, highlighting its distinct role from c-Src in colorectal carcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • c-Yes is a Src tyrosine kinase family member highly activated in colon carcinoma.
  • The specific role of c-Yes in colorectal cancer progression relative to c-Src remains unclear.

Purpose of the Study:

  • To elucidate the distinct functional role of c-Yes in colon carcinoma progression.
  • To investigate the molecular mechanisms underlying c-Yes-mediated oncogenic signaling.

Main Methods:

  • Utilized HT29 colon carcinoma cells for gene silencing experiments.
  • Assessed cell clustering, β-catenin localization, apoptosis, cell migration, and tumor growth in vivo (xenografts and metastasis models).
  • Evaluated the requirement of c-Yes kinase activity for its functions.

Main Results:

  • Silencing c-Yes, but not c-Src, increased cell clustering, membrane localization of β-catenin, and reduced target gene expression.
  • c-Yes depletion inhibited apoptosis, soft-agar growth, xenograft growth, cell migration, and liver metastasis formation.
  • Re-introduction of c-Yes restored transforming properties; kinase activity was essential for β-catenin localization and soft-agar growth but not migration.

Conclusions:

  • c-Yes plays a critical, distinct role in colon cancer progression, independent of c-Src.
  • c-Yes regulates specific oncogenic signaling pathways crucial for colorectal carcinoma development and metastasis.
  • c-Yes kinase activity is selectively required for certain oncogenic functions.

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