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ANGPTL1 attenuates cancer migration, invasion, and stemness through regulating FOXO3a-mediated SOX2 expression in

Ting-Yu Chang1, Kuo-Cheng Lan2, Chen-Yuan Chiu3

  • 1Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Clinical Science (London, England : 1979)
|April 27, 2022
PubMed

Insights

Angiopoietin-like protein 1 (ANGPTL1) suppresses colorectal cancer (CRC) progression and metastasis. Lower ANGPTL1 levels correlate with poor outcomes, suggesting its therapeutic potential in CRC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Angiopoietin-like protein 1 (ANGPTL1) is known to inhibit angiogenesis and cancer progression.
  • ANGPTL1 is frequently downregulated in various cancers, including colorectal cancer (CRC).
  • The specific roles of ANGPTL1 in CRC liver metastasis and cancer stemness remain unclear.

Purpose of the Study:

  • To investigate the role and molecular mechanisms of ANGPTL1 in colorectal cancer (CRC) liver metastasis and cancer stemness.
  • To determine the correlation between ANGPTL1 expression and clinical outcomes in CRC patients.

Main Methods:

  • Analysis of ANGPTL1 expression in CRC patient data using the ONCOMINE database and Human Tissue Microarray staining.
  • In vitro experiments assessing the effects of ANGPTL1 on CRC cell migration, invasion, and cancer stem cell (CSC) marker expression.
  • In vivo studies using tumor-bearing mice to evaluate the impact of ANGPTL1 overexpression on liver metastasis and tumor growth.

Main Results:

  • ANGPTL1 was found to be downregulated in CRC and inversely correlated with metastasis and poor clinical outcomes.
  • ANGPTL1 suppressed CRC cell migration, invasion, CSC marker expression, and sphere formation by enhancing FOXO3a and reducing SOX2 expression.
  • Overexpression of ANGPTL1 reduced liver metastasis, tumor growth, and tumorigenicity in mice.

Conclusions:

  • ANGPTL1 acts as a tumor suppressor in colorectal cancer, inhibiting metastasis and cancer stemness.
  • The findings highlight the ANGPTL1/FOXO3a/SOX2 pathway as a potential therapeutic target for CRC.
  • ANGPTL1 expression serves as a prognostic biomarker for CRC patients.
Keywords:
ANGPTL1FOXO3aSOX2cancer stem cellcolorectal cancerliver metastasis

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