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TGF-β signaling in liver and gastrointestinal cancers

L H Katz1, M Likhter2, W Jogunoori3

  • 1Department of Gastroenterology, Sheba Medical Center, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel.

Cancer Letters
|April 4, 2016
PubMed

Insights

Transforming Growth Factor-β (TGF-β) has complex roles in gastrointestinal and liver cancers, acting as both a suppressor and promoter. Understanding its signaling mechanisms is key to developing new cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • Transforming Growth Factor-β (TGF-β) exhibits multifaceted roles in liver and gastrointestinal cancers, including stem cell regulation, fibrosis, immune modulation, and dual functions as a tumor suppressor and progressor.
  • The precise molecular mechanisms governing the switch between these distinct TGF-β actions remain incompletely understood, posing a significant challenge in cancer research.

Purpose of the Study:

  • To review the molecular mechanisms of TGF-β signaling in colorectal, gastric, pancreatic, and liver cancers.
  • To highlight the integrated approach using The Cancer Genome Atlas (TCGA) and genetically engineered mouse models to dissect TGF-β pathway roles.
  • To discuss novel therapeutic strategies targeting the TGF-β pathway.

Main Methods:

  • Review of existing literature on TGF-β signaling pathways.
  • Analysis of data from The Cancer Genome Atlas (TCGA).
  • Examination of findings from genetically engineered mouse models relevant to TGF-β in cancer.

Main Results:

  • TGF-β signaling is context-dependent, influencing various cancer hallmarks including stemness, fibrosis, and immune evasion.
  • TCGA analyses and mouse models provide insights into the complex, often paradoxical, roles of TGF-β in different cancer types.
  • Clinical trials show promise for novel TGF-β targeting drugs.

Conclusions:

  • A comprehensive understanding of TGF-β pathway intricacies is essential for effective cancer treatment.
  • Targeting TGF-β offers a promising avenue for developing novel therapeutic strategies against gastrointestinal and liver cancers.
  • Further research into TGF-β mechanisms will expand the armamentarium against these malignancies.
Keywords:
CancersGI cancersLiver cancerTGF-β signaling

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