The role of TGF-β and Wnt signaling in gastrointestinal stem cells and cancer

Lopa Mishra, Kirti Shetty, Yi Tang, August Stuart, Stephen W. Byers

Research output: Contribution to journalReview articlepeer-review

136 Scopus citations


The past three decades have seen an unremitting quest to identify and understand gastrointestinal stem cells, their plasticity in differentiating across cell types, as well as their role in normal, regenerative, and cancer cells. A fascinating hallmark of stem cells is their ability to undergo assymetric cell division, which entails replication of the DNA followed by division of the nucleus and partitioning of the cytoplasm to yield two different daughter cells: a stem cell as well as a committed progenitor cell, the latter proliferating into differentiated progeny. We are only just beginning to understand how normally quiescent, tissue-specific stem cells interpret a vast array of signals to develop into the gastrointestinal system. These signaling pathways include the transforming growth factor-β (TGF-β) superfamily, Wnt, FGFs, Hedgehog, Hox proteins that originate from surrounding mesodermal/stromal tissue as well as endodermal/epithelial tissue. TGF-β and wnt proteins are key morphogens that ultimately influence cell division and cell fate, so that gut endodermal stem cells enter the cell cycle, and undergo cell division that ultimately leads to differentiated cells such as functional hepatocytes, gastric parietal cells, or gut epithelial cells. Disruptions and errors in this process usually lead to tissue-specific gastrointestinal cancers such as hepatocellular cancers, gastric adenocarcinomas, and colonic adenocarcinomas. An increasingly complex and coherent view of stem/progenitor cell signaling networks, which coordinate cell growth, proliferation, stress management, and survival, is helping to define the fragile areas where malignancies are likely to develop and shows promise for the development of better cancer therapies.

Original languageEnglish (US)
Pages (from-to)5775-5789
Number of pages15
Issue number37
StatePublished - Aug 29 2005
Externally publishedYes


  • Cancer
  • ELF
  • Smad
  • Stem cells
  • TGF-β
  • Wnt

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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