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TRIM27 mediates STAT3 activation at retromer-positive structures to promote colitis and colitis-associated

Hong-Xia Zhang1,2, Zhi-Sheng Xu3,4, Hen Lin1

  • 1College of Life Sciences, Wuhan University, 430072, Wuhan, China.

Nature Communications
|August 26, 2018
PubMed

Insights

This study identifies TRIM27 as a key regulator of STAT3 activation. TRIM27

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • Signal transducer and activator of transcription 3 (STAT3) is crucial for physiological processes.
  • Dysregulation of STAT3 is linked to severe diseases, notably cancer.
  • Regulatory mechanisms governing STAT3 activity remain largely unknown.

Purpose of the Study:

  • To elucidate the role of TRIM27 in the regulation of STAT3 activation.
  • To investigate the involvement of TRIM27 in IL-6-induced STAT3 signaling.
  • To determine the impact of TRIM27 on STAT3-mediated gene expression and disease development.

Main Methods:

  • Identified TRIM27 as a positive regulator of IL-6-induced STAT3 activation.
  • Investigated TRIM27 localization to retromer-positive structures.
  • Assessed the recruitment of gp130, JAK1, and STAT3 to these structures.
  • Evaluated the effects of TRIM27 overexpression and knockdown on cancer cell and tumor growth.
  • Examined the role of TRIM27 in mouse models of colitis and colitis-associated cancer.

Main Results:

  • TRIM27 acts as a critical link, recruiting gp130, JAK1, and STAT3 to retromer-positive structures for STAT3 phosphorylation.
  • Overexpression of TRIM27 enhances cancer cell and tumor growth.
  • TRIM27 deficiency impairs STAT3 activation, inflammatory cytokine production, and reduces colitis and colitis-associated cancer in mice.

Conclusions:

  • TRIM27 is a positive regulator of IL-6-induced STAT3 activation and downstream gene expression.
  • A retromer-dependent mechanism involving TRIM27 regulates STAT3 activation.
  • TRIM27 plays a significant role in inflammation and the development of inflammation-associated cancer.

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