Transforming growth factor-β in the gastrointestinal and hepatic tumor microenvironment

Bhagelu Ram Achyut, Li Yang

Research output: Contribution to journalArticlepeer-review

158 Scopus citations

Abstract

Transforming growth factor (TGF)-β is a multifunctional cytokine that has important roles in tumor formation, progression, and metastasis. TGF-β is overproduced, and its signaling is deregulated, in a variety of human tumors, including colorectal, gastric, pancreatic, and liver. Therapeutics are being developed to block TGF-β signaling. However, TGF-β also functions as a tumor suppressor in premalignant cells. It is not clear how its function changes from that of a tumor suppressor to a tumor promoter; improvements are needed in our understanding of TGF-β functions in tumor development before we can design inhibitors for use as anticancer therapies. TGF-β regulates not only different tumor-cell autonomous signaling pathways, but also interactions between tumor and host cells, through paracrine mechanisms. We review recent findings about how TGF-β is regulated and its roles in the tumor microenvironment and metastasis, with a focus on gastrointestinal cancers. Improved understanding of TGF-β regulation and how it mediates interaction between cancer epithelial cells, immune cells, and fibroblasts will provide important insights into tumor development and progression.

Original languageEnglish (US)
Pages (from-to)1167-78
Number of pages12
JournalGastroenterology
Volume141
Issue number4
DOIs
StatePublished - Oct 2011
Externally publishedYes

Keywords

  • Animals
  • Gastrointestinal Neoplasms
  • Humans
  • Inflammation Mediators
  • Liver Neoplasms
  • Neoplasm Invasiveness
  • Signal Transduction
  • Transforming Growth Factor beta
  • Tumor Microenvironment
  • Journal Article
  • Review

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