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J. Clin. Med. 2017, 6(1), 5; doi:10.3390/jcm6010005

The TGF-β/Smad4 Signaling Pathway in Pancreatic Carcinogenesis and Its Clinical Significance

Department of Pathology, New York University School of Medicine, and Langone Medical Center, New York, NY 10016, USA
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Author to whom correspondence should be addressed.
Academic Editor: Andrei Turtoi
Received: 25 October 2016 / Revised: 7 December 2016 / Accepted: 27 December 2016 / Published: 5 January 2017
(This article belongs to the Special Issue Biological and Clinical Aspects of TGF-beta in Carcinogenesis)
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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 advanced 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. View Full-Text
Keywords: TGF-β; Smad4; pancreatic ductal adenocarcinoma; prognosis; therapy TGF-β; Smad4; pancreatic ductal adenocarcinoma; prognosis; therapy
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Ahmed, S.; Bradshaw, A.-D.; Gera, S.; Dewan, M.Z.; Xu, R. The TGF-β/Smad4 Signaling Pathway in Pancreatic Carcinogenesis and Its Clinical Significance. J. Clin. Med. 2017, 6, 5.

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