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ACE2 inhibits breast cancer angiogenesis via suppressing the VEGFa/VEGFR2/ERK pathway

Qi Zhang1,2, Sihong Lu1,3, Tianfu Li1

  • 1Breast Disease Center, The First Affiliated Hospital, Sun Yat-Sen University, No.58 of Zhongshan 2nd road, Yuexiu district, Guangzhou, 510080, China.

Journal of Experimental & Clinical Cancer Research : CR
|April 27, 2019
PubMed
Abstract

Insights

Angiotensin-converting enzyme 2 (ACE2) inhibits breast cancer angiogenesis and metastasis by downregulating vascular endothelial growth factor A (VEGFa) signaling. Higher ACE2 expression correlates with improved relapse-free survival in breast cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Breast cancer angiogenesis is crucial for metastasis and survival.
  • Angiotensin-converting enzyme 2 (ACE2) inhibits angiogenesis in other cancers but its role in breast cancer is unknown.

Purpose of the Study:

  • To investigate the role of ACE2 in breast cancer angiogenesis and metastasis.
  • To elucidate the molecular mechanisms underlying ACE2's function in breast cancer.

Main Methods:

  • Bioinformatic analysis (GEPIA, GEO, TCGA, STRING) and qPCR for ACE2 expression.
  • In vitro assays (Transwell, proliferation, tube formation, wound healing) for cell migration, proliferation, and angiogenesis.
  • Western blotting for VEGFa, VEGFR2, MEK1/2, and ERK1/2 phosphorylation.
  • Zebrafish model for in vivo metastasis and angiogenesis assessment.

Main Results:

  • ACE2 expression is downregulated in breast cancer, correlating with poorer prognosis.
  • ACE2 inhibits breast cancer cell migration, proliferation, and angiogenesis in vitro.
  • ACE2 suppresses breast cancer metastasis and neo-angiogenesis in vivo.
  • ACE2 reduces VEGFa expression and inactivates the VEGFa/VEGFR2/ERK pathway.

Conclusions:

  • ACE2 acts as a tumor suppressor in breast cancer.
  • ACE2 inhibits breast cancer angiogenesis and metastasis via the VEGFa/VEGFR2/ERK pathway.
Keywords:
ACE2AngiogenesisBreast cancerERKVEGFR2VEGFa

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