Xia Xiang, Wu Weidong, Huang Chen, Cen Gang, Jiang Tao, Cao Jun, Huang Kejian, Qiu Zhengjun
Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, 100 Hai Ning Road, Shanghai, 200080, People's Republic of China.
Tumour Biol. 2015 Jan;36(1):111-9. doi: 10.1007/s13277-014-2883-z. Epub 2014 Dec 3.
Transforming growth factor-β (TGF-β) regulates cell functions and has key roles in pancreatic cancer development. SMAD4, as one of the Smads family of signal transducer from TGF-β, 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-β and its dual role of tumor-suppressive and tumor-promoting efforts in pancreatic cancer initiation and progression through SMAD4-dependent TGF-β signaling and SMAD4-independent TGF-β 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.
转化生长因子-β(TGF-β)调节细胞功能,在胰腺癌发展中起关键作用。SMAD4作为TGF-β信号转导的Smads家族成员之一,介导胰腺细胞增殖和凋亡,并且在一半的晚期胰腺癌中特异性失活。近年来,许多关于SMAD4的进展试图通过依赖SMAD4的TGF-β信号通路和不依赖SMAD4的TGF-β信号通路,阐明TGF-β复杂的信号传导机制及其在胰腺癌起始和进展中的肿瘤抑制和肿瘤促进双重作用。同时,几项研究对其基于手术样本免疫组化表达的潜在预后价值报道不一,且缺乏系统分析。本综述旨在探讨这种主要蛋白质的结构、功能、调节及其在确定胰腺癌进展和预后方面的作用。