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Cross talk between receptor guanylyl cyclase C and c-src tyrosine kinase regulates colon cancer cell cytostasis

Nirmalya Basu1, Rashna Bhandari, Vivek T Natarajan

  • 1Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.

Molecular and Cellular Biology
|July 22, 2009
PubMed

Insights

Increased c-src activity in colorectal cancer hinders Guanylyl cyclase C (GC-C) function, promoting cancer progression. This study reveals a novel feed-forward mechanism involving c-src and GC-C, offering new therapeutic targets for colon cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Elevated c-src kinase activity correlates with poor prognosis in colorectal cancer.
  • Guanylyl cyclase C (GC-C) is a cell surface receptor involved in regulating cell proliferation, but its role in cancer progression is complex.
  • Persistent GC-C expression in colorectal tumors suggests a role in malignancy.

Purpose of the Study:

  • To investigate the interaction between c-src and Guanylyl cyclase C (GC-C) in colorectal cancer.
  • To elucidate the functional consequences of this interaction on cellular signaling and proliferation.
  • To identify potential therapeutic targets based on the c-src/GC-C pathway.

Main Methods:

  • Western blotting and immunoprecipitation to assess protein interactions and phosphorylation.
  • Measurement of cyclic GMP (cGMP) production in response to GC-C ligands.
  • Cell-based assays to evaluate cell cycle control and proliferation.

Main Results:

  • c-src directly phosphorylates GC-C, inhibiting its ability to produce cGMP.
  • Active c-src overcomes GC-C-mediated cell cycle inhibition in colon cells.
  • Phosphorylated GC-C binds to the c-src SH2 domain, leading to further c-src activation, establishing a feed-forward loop.

Conclusions:

  • A novel cross-talk mechanism exists between the receptor guanylyl cyclase C and the tyrosine kinase c-src.
  • This feed-forward activation loop of c-src contributes to colorectal cancer progression.
  • Targeting this interaction may offer new therapeutic strategies for colorectal cancer treatment.

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