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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2017

Open Access 01-12-2017 | Research

Heat shock factor 1 inhibits the mitochondrial apoptosis pathway by regulating second mitochondria-derived activator of caspase to promote pancreatic tumorigenesis

Authors: Wenjin Liang, Yong Liao, Jing Zhang, Qi Huang, Wei Luo, Jidong Yu, Jianhua Gong, Yi Zhou, Xuan Li, Bo Tang, Songqing He, Jinghong Yang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2017

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Abstract

Background

As a relatively conservative transcriptional regulator in biological evolution, heat shock factor 1 (HSF1) is activated by, and regulates the expression of heat shock proteins (HSPs) in response to a variety of stress conditions. HSF1 also plays a key role in regulating the development of various tumors; however, its role in pancreatic cancer and the specific underlying mechanism are not clear.

Methods

We first examined HSF1 expression in pancreatic cancer tissues by immunohistochemistry, and then studied its clinical significance. We then constructed HSF1-siRNA to investigate the potential of HSF1 to regulate apoptosis, proliferation and the cell cycle of pancreatic cancer cells and the underlying mechanism both in vitro and in vivo. Protein chip analysis was used subsequently to explore the molecular regulation pathway. Finally, second mitochondria-derived activator of caspase (SMAC)-siRNA was used to validate the signaling pathway.

Results

HSF1 was highly expressed in pancreatic cancer tissues and the level of upregulation was found to be closely related to the degree of pancreatic cancer differentiation and poor prognosis. After HSF1-silencing, we found that pancreatic cancer cell proliferation decreased both in vitro and in vivo and the apoptotic cell ratio increased, while the mitochondrial membrane potential decreased, and the cells were arrested at the G0/G1 phase. In terms of the molecular mechanism, we confirmed that HSF1 regulated SMAC to inhibit mitochondrial apoptosis in pancreatic cancer cells, and to promote the occurrence of pancreatic tumors. SMAC silencing reversed the effects of HSF1 silencing.

Conclusion

Our study provides evidence that HSF1 functions as a novel oncogene in pancreatic tumors and is implicated as a target for the diagnosis and treatment of pancreatic cancer.
Appendix
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Metadata
Title
Heat shock factor 1 inhibits the mitochondrial apoptosis pathway by regulating second mitochondria-derived activator of caspase to promote pancreatic tumorigenesis
Authors
Wenjin Liang
Yong Liao
Jing Zhang
Qi Huang
Wei Luo
Jidong Yu
Jianhua Gong
Yi Zhou
Xuan Li
Bo Tang
Songqing He
Jinghong Yang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2017
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-017-0537-x

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