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

• Published in: Molecular and cellular biochemistry 2019-01, Vol.450 (1-2), p.53
• Main Authors: Ji, Yi-Fei, Li, Tao, Jiang, Feng, Ni, Wen-Kai, Guan, Cheng-Qi, Liu, Zhao-Xiu, Lu, Cui-Hua, Ni, Run-Zhou, Wu, Wei, Xiao, Ming-Bing
• Format: Article
• Language: English
• Subjects: Apoptosis; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Female; Humans; Male; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; S100 Proteins - genetics; S100 Proteins - metabolism; Signal Transduction; Smad4 Protein - genetics; Smad4 Protein - metabolism; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism
• ISSN: 1573-4919
• DOI: 10.1007/s11010-018-3372-2

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-β /SMAD4/p21 pathway. S100A11 and TGF-β protein expressions in 30 paraffin-embedded specimens were evaluated by immunohistochemistry. S100A11 and TGF-β 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-β expression in pancreatic cancerous tissue. Silencing TGF-β down-regulated intracellular P21 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-β and SMAD4 expression. Our findings revealed that S100A11 and TGF-β /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.