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Hes1 Increases the Invasion Ability of Colorectal Cancer Cells via the STAT3-MMP14 Pathway

M T Weng1,2,3, P N Tsao4, H L Lin3

  • 1Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei, Taiwan.

Plos One
|December 10, 2015
PubMed

Insights

Hairy/enhancer of split 1 (Hes1) promotes colorectal cancer (CRC) invasion via the STAT3-MMP14 pathway. High Hes1 expression predicts poor prognosis in CRC patients, suggesting Hes1 as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The Notch pathway is implicated in tumor-initiating cell self-renewal and colorectal cancer (CRC) development.
  • Hairy/enhancer of split (HES) proteins, key Notch targets, are involved in various cancers.
  • Deregulated Notch1 and Jagged1 expression is noted in CRC.

Purpose of the Study:

  • To investigate the role of Hes1 in colorectal cancer tumorigenesis.
  • To elucidate the molecular mechanisms by which Hes1 influences CRC progression.
  • To evaluate Hes1 as a prognostic biomarker in CRC.

Main Methods:

  • Functional assays involving Hes1 knockdown and overexpression in CRC cells.
  • Analysis of STAT3 phosphorylation and MMP14 protein levels.
  • Correlation analysis of Hes1 mRNA expression with patient prognosis.

Main Results:

  • Hes1 knockdown induced CRC cell senescence and reduced invasion.
  • Hes1 overexpression increased STAT3 phosphorylation and MMP14 levels.
  • High Hes1 mRNA expression in human CRC correlated with poor prognosis.

Conclusions:

  • Hes1 promotes CRC cell invasion through the STAT3-MMP14 pathway.
  • Hes1 expression level is a significant predictor of poor prognosis in colorectal cancer patients.
  • Targeting Hes1 may offer a therapeutic strategy for CRC.

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