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Decreased CHK protein levels are associated with Src activation in colon cancer cells

S Zhu1, J D Bjorge, H C Cheng

  • 1Department of Biochemistry and Molecular Biology, and Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.

Oncogene
|October 16, 2007
PubMed

Insights

Csk-homologous kinase (CHK) is expressed in colon cells and its decreased levels correlate with increased Src activity in colon cancer. CHK suppresses colon cancer cell growth and invasion, revealing its role in tumorigenicity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Src activation is linked to colon cancer, but its activation mechanism is unclear.
  • Csk-homologous kinase (CHK) inhibits Src kinase activity through phosphorylation and non-catalytic mechanisms.
  • CHK was previously thought to be primarily in brain and hematopoietic cells.

Purpose of the Study:

  • To investigate the role of CHK in colon cancer.
  • To determine CHK expression in normal and cancerous colon cells and tissues.
  • To explore the mechanism of CHK's action on Src and its effect on colon cancer cell behavior.

Main Methods:

  • Western blotting to assess CHK and C-terminal Src kinase protein levels.
  • Immunofluorescence microscopy to visualize CHK and Src colocalization.
  • Overexpression studies in colon cancer cells to evaluate Src activity and cell growth/invasion.

Main Results:

  • CHK is expressed in normal colon cell lines and tissues, but its levels are significantly decreased in colon cancer cell lines and tissues.
  • Decreased CHK levels correlate with increased Src activity in colon cancer cells.
  • Overexpression of CHK inactivates Src, suppresses anchorage-independent growth, and reduces cell invasion in colon cancer cells, independent of Y530 phosphorylation.

Conclusions:

  • CHK plays a significant role in regulating Src activity in colon cells.
  • Reduced CHK expression is associated with colon cancer progression and tumorigenicity.
  • CHK represents a potential therapeutic target for colon cancer treatment.

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