Tumor Biology

, Volume 36, Issue 1, pp 111–119 | Cite as

SMAD4 and its role in pancreatic cancer

  • Xiang Xia
  • Weidong Wu
  • Chen Huang
  • Gang Cen
  • Tao Jiang
  • Jun Cao
  • Kejian Huang
  • Zhengjun Qiu


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.


Pancreatic cancer TGF-β signaling pathway Loss of SMAD4 Prognosis 



This study was supported by grants from the National Natural Science Foundation of China (No. 81372640 (to QZJ)) and (No. 81101844 and No. 81210108027 (to C. Huang)), Shanghai Municipal Human Resources and Social Security Bureau (No. 2012040 and No. 13PJD024 (to C. Huang)), and Shanghai Municipal Health Bureau (No. XYQ2013092 (to C. Huang)). This is an original article and is not being considered for publication elsewhere. All of the authors contributed to the article and are aware of and agree to its submission for publication.

Conflicts of interest


Author’s contribution

XX, WW, CH, GC, TJ, and JC conceived and designed the study. XX, KH, and ZQ performed the experiments. XX and WW analyzed the data. XX and ZQ wrote the manuscript. All authors read and approved the final manuscript.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Xiang Xia
    • 1
  • Weidong Wu
    • 1
  • Chen Huang
    • 1
  • Gang Cen
    • 1
  • Tao Jiang
    • 1
  • Jun Cao
    • 1
  • Kejian Huang
    • 1
  • Zhengjun Qiu
    • 1
  1. 1.Department of General SurgeryShanghai Jiaotong University Affiliated First People’s HospitalShanghaiPeople’s Republic of China

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