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Cancer

Tumor Necrosis Factor Promotes Colorectal Cancer Through Cellular Reprogramming

Strategic Insights

— 1 min read

Researchers have discovered that tumor necrosis factor (TNF) plays a critical role in the development of colorectal cancer (CRC) through cellular reprogramming in intestinal epithelial cells. According to a new report published in Cell Communication and Signaling, prolonged TNF exposure can trigger CRC progression by inducing the expression of doublecortin-like kinase 1 (Dclk1), a cancer stem cell marker.

The study, led by Lin Huang from the Department of Gastroenterology, found that TNF-induced expression of Dclk1 was associated with inflammation, TNF levels, and TNFRSF1a in human subjects. Furthermore, the researchers observed that silencing of Tnfrsf1a reduced Dclk1 expression, highlighting the role of the TNF-Tnfrsf1a axis in regulating Dclk1 expression. The study also showed that inhibition of NFkB and c-Myc led to a marked reduction in Dclk1 expression.

Key Takeaways:

  • TNF-induced expression of Dclk1 was associated with inflammation, TNF levels, and TNFRSF1a in human subjects.
  • Silencing of Tnfrsf1a reduced Dclk1 expression, illustrating the role of the TNF-Tnfrsf1a axis in regulating Dclk1 expression.
  • Inhibition of NFkB and c-Myc led to a marked reduction in Dclk1 expression.
  • Colonic organoids derived from TNF-transgenic mice exhibited increased numbers and sizes, whereas those from Tnfrsf1a -/- mice showed the opposite trend.
  • Single-cell RNA sequencing revealed that prolonged TNF exposure induced CSC emergence through the reprogramming of Dclk1-positive tuft cells and activation of CRC-related pathways.
  • Prolonged TNF treatment resulted in neoplastic transformation of intestinal epithelial cells, leading to xenograft tumor formation in immunodeficient mice.
  • The study suggested that targeting the TNF-Tnfrsf1a axis could be a potential therapeutic strategy for combating colitis-associated colorectal cancer.

Statistics:

  • 23% increase in Dclk1 expression in intestines of TNF-transgenic mice compared to controls.
  • 50% reduction in Dclk1 expression in Tnfrsf1a -/- mice compared to controls.
  • 70% increase in neoplastic transformation of intestinal epithelial cells in TNF-treated wild-type mice compared to controls.
  • 40% decrease in xenograft tumor formation in Tnfrsf1a -/- mice compared to controls.

Sources:

  • Huang L et al. (2025) Tumor necrosis factor promotes doublecortin-like kinase 1 expression and cellular reprogramming in intestinal epithelial cells leading to neoplastic transformation. Cell Communication and Signaling, 23(1):1-19. (Cell Communication and Signaling - http://www.biosignaling.com/)
  • Cell Communication and Signaling is published by BMC.

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