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TRIB3 Interacts with STAT3 to Promote Cancer Angiogenesis

Qian-Zhi Chen1, Yan Chen2, Xia Li3

  • 1Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Current Medical Science
|October 16, 2022
PubMed
Abstract

Insights

Tribbles pseudokinase 3 (TRIB3) promotes colon cancer angiogenesis by activating the STAT3/VEGFA pathway. Targeting TRIB3 offers a new therapeutic strategy for TRIB3-overexpressed cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Vascular endothelial growth factor A (VEGFA) drives angiogenesis, crucial for tumor growth and metastasis.
  • Identifying novel targets regulating VEGFA-mediated angiogenesis is vital for effective cancer treatment.

Purpose of the Study:

  • To investigate the role of the tribbles pseudokinase 3 (TRIB3)/signal transducer and activator of transcription 3 (STAT3)/VEGFA signaling axis in colon cancer angiogenesis.
  • To explore TRIB3 as a potential therapeutic target for colon cancer.

Main Methods:

  • Database and tissue microarray analysis to assess TRIB3 expression in colon cancer.
  • In vitro assays (CCK8, migration, tube formation) to evaluate TRIB3's effect on endothelial cells.
  • qPCR, Western blotting, immunoprecipitation, and chromatin immunoprecipitation to elucidate the TRIB3/STAT3/VEGFA regulatory mechanism.
  • In vivo animal experiments to confirm findings.

Main Results:

  • TRIB3 expression is elevated in colon cancer tissues and correlates with poor prognosis.
  • TRIB3 silencing inhibits, while overexpression promotes, colon cancer angiogenesis in vitro and in vivo.
  • TRIB3 physically interacts with STAT3, enhancing its transcriptional activity.
  • TRIB3 promotes angiogenesis by increasing VEGFA expression via the STAT3 pathway.

Conclusions:

  • The TRIB3/STAT3/VEGFA axis plays a significant role in colon cancer angiogenesis.
  • TRIB3 represents a potential therapeutic target for cancers with TRIB3 overexpression.
Keywords:
angiogenesiscancersignal transducer and activator of transcription 3tribbles pseudo-kinase 3vascular endothelial growth factor

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