Molecular and Cellular Biochemistry

, Volume 450, Issue 1–2, pp 53–64 | Cite as

Correlation between S100A11 and the TGF-β1/SMAD4 pathway and its effects on the proliferation and apoptosis of pancreatic cancer cell line PANC-1

  • Yi-Fei Ji
  • Tao Li
  • Feng Jiang
  • Wen-Kai Ni
  • Cheng-Qi Guan
  • Zhao-Xiu Liu
  • Cui-Hua Lu
  • Run-Zhou Ni
  • Wei WuEmail author
  • Ming-Bing XiaoEmail author


S100A11 as a S100 protein family member has been documented to play dual-direction regulation over cancer cell proliferation. We explored the role of S100A11 in the proliferation and apoptosis of pancreatic cancer cell line PANC-1 and the potential mechanisms involving the TGF-β1/SMAD4/p21 pathway. S100A11 and TGF-β1 protein expressions in 30 paraffin-embedded specimens were evaluated by immunohistochemistry. S100A11 and TGF-β1 expression in PANC-1 cell line was suppressed using small interfering RNA (siRNA), respectively. Subsequently, pancreatic cancer cell apoptosis was measured by Cell Counting Kit-8 and flow cytometry, and S100A11 and TGF-β1/SMAD4/p21 pathway proteins and genes were detected with Western blotting and quantitative polymerase chain reaction (qPCR). S100A11 cytoplasmic/nuclear protein translocation was examined using NE-PER® cytoplasm/nuclear protein extraction in cells interfered with TGF-β1 siRNA. Our results showed that S100A11 expression was positively correlated with TGF-β1 expression in pancreatic cancerous tissue. Silencing TGF-β1 down-regulated intracellular P21WAF1 expression by 90%, blocked S100A11 from cytoplasm entering nucleus, and enhanced cell proliferation. Silencing S100A11 down-regulated intracellular P21 expression and promoted cell apoptosis without significantly changing TGF-β1 and SMAD4 expression. Our findings revealed that S100A11 and TGF-β1/SMAD4 signaling pathway were related but mutually independent in regulating PANC-1 cells proliferation and apoptosis. Other independent mechanisms might be involved in S100A11’s regulation of pancreatic cell growth. S100A11 could be a potential gene therapy target for pancreatic cancer.


Pancreatic cancer S100A11 protein TGF-β1/SMAD4 pathway P21WAF1 Proliferation ·apoptosis 



This study was supported by Grants from the Natural Youth Science Foundation of China (Grant No. 81502055), the Natural Science Foundation of Jiangsu Province (Grant No. BK20161286), the Health Project of Jiangsu Province (Grant No. H201624) and the Social Development Foundation of Nantong City (Grant Nos. MS22016056, MS22015062, HS2014072, and MS22015044).

Author Contributions

YFJ, TL, FJ, WKN, and CQG carried out the studies, participated in collecting data, and drafted the manuscript. WW and MBX performed the statistical analysis and participated in its design. ZXL, CHL, and RZN helped to draft the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of GastroenterologyAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China
  2. 2.Department of Medical OncologyAffiliated Cancer Hospital of Nantong UniversityNantongPeople’s Republic of China
  3. 3.Research Center of Clinical MedicineAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China
  4. 4.Department of Gastroenterology and Research Center of Clinical MedicineAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China

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