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TNFAIP8 protein functions as a tumor suppressor in inflammation-associated colorectal tumorigenesis

Yunwei Lou1,2, Xueqin Tian3,4, Chen Sun5

  • 1Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Medical University, 453003, Xinxiang, Henan, China. ylou@xxmu.edu.cn.

Cell Death & Disease
|April 7, 2022
PubMed

Insights

Tumor necrosis factor-α-induced protein 8 (TIPE) suppresses colon cancer. Loss of TIPE worsens colitis and promotes tumor growth, indicating TIPE is a tumor suppressor in the intestine.

Area of Science:

  • Oncology
  • Immunology
  • Gastroenterology

Background:

  • Tumor necrosis factor-α-induced protein 8 (TNFAIP8 or TIPE) is a protein with unclear roles in carcinogenesis.
  • Previous understanding suggested TIPE might be pro-cancerous, but its specific function in intestinal cancers remained elusive.

Purpose of the Study:

  • To investigate the role of TIPE in colitis and colitis-associated colon cancer.
  • To elucidate the mechanisms by which TIPE influences intestinal inflammation and tumor development.

Main Methods:

  • Genetic deletion of TIPE in mice (Tipe-/-) to study its effects on chemical-induced colitis and colon cancer.
  • Analysis of inflammatory responses, gut microbiota, NF-κB and STAT3 activation, and intestinal epithelial cell proliferation and DNA damage.
  • Investigation of the role of colon microbiota and the non-hematopoietic compartment in TIPE's function.
  • Analysis of TIPE expression and its correlation with patient survival in human colorectal cancers.

Main Results:

  • Genetic deletion of TIPE exacerbated chemical-induced colitis and colitis-associated colon cancer in mice.
  • Loss of TIPE led to increased inflammatory responses, dysbiosis, NF-κB and STAT3 activation, and accelerated dysplasia, DNA damage, and proliferation.
  • Colon microbiota were crucial for enhanced tumor growth in Tipe-/- mice.
  • TIPE's tumor-suppressive function was primarily attributed to the non-hematopoietic compartment.
  • TIPE was downregulated in human colorectal cancers, with low Tipe mRNA levels correlating with reduced patient survival.

Conclusions:

  • TIPE acts as a tumor suppressor in the context of colitis-associated colon cancer.
  • TIPE modulates intestinal inflammation and carcinogenesis, partly through its effects on microbiota and epithelial cell dynamics.
  • Downregulation of TIPE in human colorectal cancer suggests its potential as a prognostic biomarker and therapeutic target.

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