Knockdown GREM1 suppresses cell growth, angiogenesis, and epithelial-mesenchymal transition in colon cancer

Yan Liu1, Yongchao Li2, Ruizhe Hou3,3

  • 1Department of Ultrasonography, China-Japan Union Hospital, Jilin University, Changchun, China.

Insights

Gremlin 1 (GREM1) is overexpressed in colorectal cancer (CRC) and drives tumor growth and metastasis. Inhibiting GREM1 shows promise for CRC therapy and improving patient prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Gremlin 1 (GREM1) is a known bone morphogenetic protein (BMP) antagonist and vascular endothelial growth factor receptor-2 (VEGFR2) agonist.
  • GREM1 is overexpressed in colorectal cancer (CRC) tissues, but its specific role in carcinogenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of GREM1 in colorectal cancer (CRC) development, progression, and potential as a therapeutic target.

Main Methods:

  • Comparative analysis of GREM1 expression in different colon cancer cell lines and CRC tissues using Gene Expression Omnibus (GEO) databases.
  • Functional studies involving GREM1 silencing via short hairpin RNA (shRNA) in CRC cells.
  • Assessment of GREM1's impact on cell proliferation, migration, epithelial-mesenchymal transition (EMT), and angiogenesis.
  • Combination therapy evaluation with a vascular endothelial growth factor (VEGF) inhibitor.

Main Results:

  • GREM1 expression was significantly higher in mesenchymal-like CRC cells and primary CRC tissues compared to normal cells and tissues.
  • GREM1 overexpression correlated with lower histological grade and stage 2-3 metastatic recurrence in CRC.
  • GREM1 silencing inhibited CRC cell proliferation, migration, EMT, and VEGF-induced angiogenesis.
  • GREM1 silencing repressed key signaling pathways including BMP, VEGF, and CXCL12.
  • Combined GREM1 inhibition and VEGF inhibition demonstrated enhanced anti-angiogenic effects.

Conclusions:

  • GREM1 plays a significant role in colorectal cancer (CRC) development and progression.
  • GREM1 is a potential biomarker for CRC diagnosis and prognosis.
  • Targeting GREM1, potentially in combination with anti-VEGF therapies, offers a novel strategy for CRC treatment.

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