Document Type

Journal Article

Publication Date

1-2018

Journal

International Journal of Biological Sciences

Volume

14

Issue

2

Inclusive Pages

111-123

DOI

10.7150/ijbs.23230

Abstract

Transforming growth factor β (TGF-β) 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-β 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.

Comments

Reproduced with permission of Ivyspring Publishing. International Journal of Biological Sciences

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Peer Reviewed

1

Open Access

1

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