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GRHL2 inhibits colorectal cancer progression and metastasis via oppressing epithelial-mesenchymal transition

Zhou Yang1, Dejun Wu1, Yusheng Chen1

  • 1Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center , Shanghai , China.

Cancer Biology & Therapy
|May 8, 2019
PubMed

Insights

Grainyhead-like 2 (GRHL2) and ZEB1 suppress colorectal cancer (CRC) progression and metastasis by inhibiting epithelial-mesenchymal transition (EMT). GRHL2 knockdown promotes CRC cell migration, invasion, and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Colorectal cancer (CRC) progression is linked to epithelial-mesenchymal transition (EMT).
  • Grainyhead-like 2 (GRHL2) has been previously shown to inhibit CRC cell proliferation by targeting ZEB1.

Purpose of the Study:

  • To investigate the role of GRHL2 in promoting CRC progression and metastasis via EMT.
  • To elucidate the relationship between GRHL2 and ZEB1 in regulating CRC cell behavior.

Main Methods:

  • Generation of GRHL2-overexpressing and GRHL2-knockdown CRC cell lines.
  • Analysis of EMT markers (E-cadherin, Vimentin, β-catenin, ZO-1, ZEB1) using qRT-PCR, Western blotting, and immunofluorescence.
  • In vitro assays (Transwell, wound healing) and in vivo mouse tail vein injection model to assess migration, invasion, and metastasis.

Main Results:

  • GRHL2 overexpression induced mesenchymal-epithelial transition (MET) with increased epithelial markers and decreased mesenchymal markers.
  • GRHL2 knockdown promoted EMT, increasing migration, invasion, and metastasis in vitro and in vivo.
  • GRHL2 and ZEB1 expression were inversely correlated; ZEB1 knockdown partially rescued the effects of GRHL2 knockdown.

Conclusions:

  • The GRHL2/ZEB1 axis plays a crucial role in inhibiting CRC progression and metastasis.
  • Suppressing EMT through the GRHL2/ZEB1 pathway represents a potential therapeutic strategy for colorectal cancer.
Keywords:
Grainyhead-like 2ZEB1colorectal cancerepithelial-mesenchymal transitionmesenchymal-epithelial transition

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