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Publication : The role of TGF-β/SMAD4 signaling in cancer.

First Author  Zhao M Year  2018
Journal  Int J Biol Sci Volume  14
Issue  2 Pages  111-123
PubMed ID  29483830 Mgi Jnum  J:320764
Mgi Id  MGI:6878672 Doi  10.7150/ijbs.23230
Citation  Zhao M, et al. (2018) The role of TGF-beta/SMAD4 signaling in cancer. Int J Biol Sci 14(2):111-123
abstractText  Transforming growth factor beta (TGF-beta) signaling pathway plays important roles in many biological processes, including cell growth, differentiation, apoptosis, migration, as well as cancer initiation and progression. SMAD4, which serves as the central mediator of TGF-beta signaling, is specifically inactivated in over half of pancreatic duct adenocarcinoma, and varying degrees in many other types of cancers. In the past two decades, multiple studies have revealed that SMAD4 loss on its own does not initiate tumor formation, but can promote tumor progression initiated by other genes, such as KRAS activation in pancreatic duct adenocarcinoma and APC inactivation in colorectal cancer. In other cases, such as skin cancer, loss of SMAD4 plays an important initiating role by disrupting DNA damage response and repair mechanisms and enhance genomic instability, suggesting its distinct roles in different types of tumors. This review lists SMAD4 mutations in various types of cancer and summarizes recent advances on SMAD4 with focuses on the function, signaling pathway, and the possibility of SMAD4 as a prognostic indicator.
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