TY - JOUR
T1 - The TGF-β/Smad4 signaling pathway in pancreatic carcinogenesis and its clinical significance
AU - Ahmed, Sunjida
AU - Bradshaw, Azore Dee
AU - Gera, Shweta
AU - Zahidunnabi Dewan, M.
AU - Xu, Ruliang
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Pancreatic ductal adenocarcinoma
KW - Prognosis
KW - Smad4
KW - TGF-β
KW - Therapy
UR - http://www.scopus.com/inward/record.url?scp=85048803226&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85048803226&partnerID=8YFLogxK
U2 - 10.3390/jcm6010005
DO - 10.3390/jcm6010005
M3 - Review article
SN - 2077-0383
VL - 6
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 1
ER -