Alterations in the Smad pathway in human cancers

Debangshu Samanta, Pran K. Datta

Research output: Contribution to journalReview articlepeer-review

44 Scopus citations


Members of the TGF-beta superfamily exhibit various biological activities, and perturbations of their signaling are linked to certain clinical disorders including cancer. The role of TGF-beta signaling as a tumor suppressor pathway is best illustrated by the presence of inactivating mutations in genes encoding TGF-beta receptors and Smads in human carcinomas. This perspective is further supported by studies of tumor development in mouse models after modulation of receptors and Smads. TGF-beta also controls processes such as cell invasion, immune regulation, and microenvironment alterations that cancer cells may exploit to their advantage for their progression. Consequently, the output of a TGF-beta response is highly situation dependent, across different tissues, and also in cancer in general. Understanding the mechanisms of TGF-beta superfamily signaling is thus important for the development of new ways to treat various types of cancer. This review focuses on recent advances in understanding the Smad dependent TGF-beta pathway as it relates to human carcinogenesis.

Original languageEnglish (US)
Pages (from-to)1281-1293
Number of pages13
JournalFrontiers in Bioscience
Issue number4
StatePublished - Jan 1 2012
Externally publishedYes


  • Cancer
  • Neoplasia
  • Review
  • Smads
  • TGF-β
  • Tumor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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