SMAD4 and its role in pancreatic cancer

被引:82
作者
Xia, Xiang [1 ]
Wu, Weidong [1 ]
Huang, Chen [1 ]
Cen, Gang [1 ]
Jiang, Tao [1 ]
Cao, Jun [1 ]
Huang, Kejian [1 ]
Qiu, Zhengjun [1 ]
机构
[1] Shanghai Jiao Tong Univ, Peoples Hosp 1, Dept Gen Surg, Shanghai 200080, Peoples R China
基金
中国国家自然科学基金;
关键词
Pancreatic cancer; TGF-beta signaling pathway; Loss of SMAD4; Prognosis; GROWTH-FACTOR-BETA; EPITHELIAL-MESENCHYMAL TRANSITION; PAPILLARY-MUCINOUS NEOPLASMS; DUCTAL ADENOCARCINOMA; INTRAEPITHELIAL NEOPLASIA; CELL-LINES; DPC4; GENE; IN-VITRO; K-RAS; DPC4/SMAD4; EXPRESSION;
D O I
10.1007/s13277-014-2883-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Transforming growth factor-beta (TGF-beta) regulates cell functions and has key roles in pancreatic cancer development. SMAD4, as one of the Smads family of signal transducer from TGF-beta, mediates pancreatic cell proliferation and apoptosis and is specifically inactivated in half of advanced pancreatic cancers. In recent years, many advances concerning SMAD4 had tried to unravel the complex signaling mechanisms of TGF-beta and its dual role of tumor-suppressive and tumor-promoting efforts in pancreatic cancer initiation and progression through SMAD4-dependent TGF-beta signaling and SMAD4-independent TGF-beta signaling pathways. Meanwhile, its potential prognostic value based on immunohistochemical expression in surgical sample was variably reported by several studies and short of a systematic analysis. This review aimed to discuss the structure, functions, and regulation of this principal protein and its effects in determining the progression and prognosis of pancreatic cancer.
引用
收藏
页码:111 / 119
页数:9
相关论文
共 95 条
[1]   Role of transforming growth factor-beta in growth and injury response of the pancreatic duct epithelium in vitro [J].
Alvarez, C ;
Bass, BL .
JOURNAL OF GASTROINTESTINAL SURGERY, 1999, 3 (02) :178-184
[2]   Reassessment of K-ras mutations at codon 12 by direct PCR and sequencing from tissue microdissection in human pancreatic adenocarcinomas [J].
Aoki, Y ;
Hosaka, S ;
Tachibana, N ;
Karasawa, Y ;
Kawa, S ;
Kiyosawa, K .
PANCREAS, 2000, 21 (02) :152-157
[3]   Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer [J].
Bardeesy, Nabeel ;
Cheng, Kuang-hung ;
Berger, Justin H. ;
Chu, Gerald C. ;
Pahler, Jessica ;
Olson, Peter ;
Hezel, Aram F. ;
Horner, James ;
Lauwers, Gregory Y. ;
Hanahan, Douglas ;
DePinho, Ronald A. .
GENES & DEVELOPMENT, 2006, 20 (22) :3130-3146
[4]   Effects of Activin and TGFβ on p21 in Colon Cancer [J].
Bauer, Jessica ;
Sporn, Judith C. ;
Cabral, Jennifer ;
Gomez, Jessica ;
Jung, Barbara .
PLOS ONE, 2012, 7 (06)
[5]   Aberrant p16INK4A and DPC4/Smad4 expression in intraductal papillary mucinous tumours of the pancreas is associated with invasive ductal adenocarcinoma [J].
Biankin, AV ;
Biankin, SA ;
Kench, JG ;
Morey, AL ;
Lee, CS ;
Head, DR ;
Eckstein, RP ;
Hugh, TB ;
Henshall, SM ;
Sutherland, RL .
GUT, 2002, 50 (06) :861-868
[6]   DPC4/Smad4 expression and outcome in pancreatic ductal adenocarcinoma [J].
Biankin, AV ;
Morey, AL ;
Lee, CS ;
Kench, JG ;
Biankin, SA ;
Hook, HC ;
Head, DR ;
Hugh, TB ;
Sutherland, RL ;
Henshall, SM .
JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (23) :4531-4542
[7]   Validation of the 6th Edition AJCC Pancreatic Cancer Staging System - Report from the National Cancer Database [J].
Bilimoria, Karl Y. ;
Bentrem, David J. ;
Ko, Clifford Y. ;
Ritchey, Jamie ;
Stewart, Andrew K. ;
Winchester, David P. ;
Talamonti, Mark S. .
CANCER, 2007, 110 (04) :738-744
[8]   Inhibition of transforming growth factor-β signaling in human cancer:: Targeting a tumor suppressor network as a therapeutic strategy [J].
Biswas, Swati ;
Criswell, Tracy L. ;
Wang, Shizhen Emily ;
Arteaga, Carlos L. .
CLINICAL CANCER RESEARCH, 2006, 12 (14) :4142-4146
[9]   SMAD4 Gene Mutations Are Associated with Poor Prognosis in Pancreatic Cancer [J].
Blackford, Amanda ;
Serrano, Oscar K. ;
Wolfgang, Christopher L. ;
Parmigiani, Giovanni ;
Jones, Sian ;
Zhang, Xiaosong ;
Parsons, D. Williams ;
Lin, Jimmy Cheng-Ho ;
Leary, Rebecca J. ;
Eshleman, James R. ;
Goggins, Michael ;
Jaffee, Elizabeth M. ;
Iacobuzio-Donahue, Christine A. ;
Maitra, Anirban ;
Cameron, John L. ;
Olino, Kelly ;
Schulick, Richard ;
Winter, Jordan ;
Herman, Joseph M. ;
Laheru, Daniel ;
Klein, Alison P. ;
Vogelstein, Bert ;
Kinzler, Kenneth W. ;
Velculescu, Victor E. ;
Hruban, Ralph H. .
CLINICAL CANCER RESEARCH, 2009, 15 (14) :4674-4679
[10]   A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition [J].
Bracken, Cameron P. ;
Gregory, Philip A. ;
Kolesnikoff, Natasha ;
Bert, Andrew G. ;
Wang, Jun ;
Shannon, M. Frances ;
Goodall, Gregory J. .
CANCER RESEARCH, 2008, 68 (19) :7846-7854