Alterations in the Smad pathway in human cancers.
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.
Departments of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Debangshu
D
Samanta
Pran K
PK
Datta
D000818:Animals; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009369:Neoplasms / Q000378:metabolism*; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D015854:Up-Regulation
D051785:Smad Proteins; D016212:Transforming Growth Factor beta