The TGF-β/Smad4 signaling pathway in pancreatic carcinogenesis and its clinical significance

Sunjida Ahmed, Azore Dee Bradshaw, Shweta Gera, M. Zahidunnabi Dewan, Ruliang Xu

Research output: Contribution to journalReview article

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human cancers due to its complicated genomic instability. PDAC frequently presents at an advanced stage with extensive metastasis, which portends a poor prognosis. The known risk factors associated with PDAC include advasnced age, smoking, long-standing chronic pancreatitis, obesity, and diabetes. Its association with genomic and somatic mutations is the most important factor for its aggressiveness. The most common gene mutations associated with PDAC include KRas2, p16, TP53, and Smad4. Among these, Smad4 mutation is relatively specific and its inactivation is found in more than 50% of invasive pancreatic adenocarcinomas. Smad4 is a member of the Smad family of signal transducers and acts as a central mediator of transforming growth factor beta (TGF-β) signaling pathways. The TGF-β signaling pathway promotes many physiological processes, including cell growth, differentiation, proliferation, fibrosis, and scar formation. It also plays a major role in the development of tumors through induction of angiogenesis and immune suppression. In this review, we will discuss the molecular mechanism of TGF-β/Smad4 signaling in the pathogenesis of pancreatic adenocarcinoma and its clinical implication, particularly potential as a prognostic factor and a therapeutic target.

Original languageEnglish (US)
JournalJournal of Clinical Medicine
Volume6
Issue number1
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

Transforming Growth Factor beta
Carcinogenesis
Adenocarcinoma
Mutation
Physiological Phenomena
Genomic Instability
Chronic Pancreatitis
Transducers
Cicatrix
Cell Differentiation
Neoplasms
Fibrosis
Obesity
Smoking
Neoplasm Metastasis
Genes

Keywords

  • Pancreatic ductal adenocarcinoma
  • Prognosis
  • Smad4
  • TGF-β
  • Therapy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The TGF-β/Smad4 signaling pathway in pancreatic carcinogenesis and its clinical significance. / Ahmed, Sunjida; Bradshaw, Azore Dee; Gera, Shweta; Zahidunnabi Dewan, M.; Xu, Ruliang.

In: Journal of Clinical Medicine, Vol. 6, No. 1, 01.01.2017.

Research output: Contribution to journalReview article

Ahmed, Sunjida ; Bradshaw, Azore Dee ; Gera, Shweta ; Zahidunnabi Dewan, M. ; Xu, Ruliang. / The TGF-β/Smad4 signaling pathway in pancreatic carcinogenesis and its clinical significance. In: Journal of Clinical Medicine. 2017 ; Vol. 6, No. 1.
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