HSF1 upregulates ATG4B expression and enhances epirubicin-induced protective autophagy in hepatocellular carcinoma cells.

Abstract:

:Considerable evidences have shown that both heat shock transcription factor 1 (HSF1) and autophagy can attenuate the sensitivity of hepatocellular carcinoma (HCC) cells to chemotherapeutic reagents. However, it is still little known whether HSF1 is associated with autophagy in regulating the chemosensitivity of HCC cells. In this study, we for the first time demonstrated that HSF1 markedly attenuated the killing effect of epirubicin (EPI) to HCC cells via enhancing the EPI-induced protective autophagy. Mechanistically, HSF1 upregulated autophagy related 4B (ATG4B) in HCC cells, which enhanced the EPI-triggered protective autophagy. Reporter assay showed that HSF1 increased the transcriptional activity of ATG4B gene promoter, and chromatin immunoprecipitation assay verified that HSF1 bound to the site (-1429 to -1417) in ATG4B gene promoter region. The experiments in nude mice showed that knockdown of HSF1 or ATG4B strengthened the anti-HCC effect of EPI in vivo. Collectively, these results revealed that HSF1 elevates ATG4B via promoting its transcription, which alleviates the sensitivity of EPI in HCC cells through enhancing protective autophagy, suggesting that the "HSF1/ATG4B/protective autophagy" pathway may be a novel target for developing sensitizing strategy to HCC chemotherapy.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Zhang N,Wu Y,Lyu X,Li B,Yan X,Xiong H,Li X,Huang G,Zeng Y,Zhang Y,Lian J,Ni Z,He F

doi

10.1016/j.canlet.2017.08.039

subject

Has Abstract

pub_date

2017-11-28 00:00:00

pages

81-90

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(17)30534-7

journal_volume

409

pub_type

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