Cigliano, Antonio and Wang, Chunmei and Pilo, Maria G. and Szydlowska, Marta and Brozzetti, Stefania and Latte, Gavinella and Pes, Giovanni M. and Pascale, Rosa M. and Seddaiu, Maria A. and Vidili, Gianpaolo and Ribback, Silvia and Dombrowski, Frank and Evert, Matthias and Chen, Xin and Calvisi, Diego F. (2017) Inhibition of HSF1 suppresses the growth of hepatocarcinoma cell lines in vitro and AKT-driven hepatocarcinogenesis in mice. ONCOTARGET, 8 (33). pp. 54149-54159. ISSN 1949-2553,
Full text not available from this repository. (Request a copy)Abstract
Upregulation of the heat shock transcription factor 1 (HSF1) has been described as a frequent event in many cancer types, but its oncogenic role in hepatocellular carcinoma (HCC) remains poorly delineated. In the present study, we assessed the function(s) of HSF1 in hepatocarcinogenesis via in vitro and in vivo approaches. In particular, we determined the importance of HSF1 on v-Akt murine thymoma viral oncogene homolog (AKT)-induced liver cancer development in mice. We found that knockdown of HSF1 activity via specific siRNA triggered growth restraint by suppressing cell proliferation and inducing massive cell apoptosis in human HCC cell lines. At the molecular level, HSF1 inhibition was accompanied by downregulation of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) cascade and related metabolic pathways. Most importantly, overexpression of a dominant negative form of HSF1 (HSF1dn) in the mouse liver via hydrodynamic gene delivery led to the inhibition of mouse hepatocarcinogenesis driven by overexpression of AKT. In human liver cancer specimens, we detected that HSF1 is progressively induced from human non-tumorous surrounding livers to HCC, reaching the highest expression in the tumors characterized by the poorest outcome (as defined by the length of patients' survival). In conclusion, HSF1 is an independent prognostic factor in liver cancer and might represent an innovative therapeutic target in HCC subsets characterized by activation of the AKT/mTOR pathway.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEAT-SHOCK FACTOR-1; FATTY-ACID SYNTHASE; HEPATOCELLULAR-CARCINOMA; TRANSCRIPTION FACTOR-1; EXPRESSION; CANCER; CHAPERONES; PROMOTES; GLUCOSE; ROLES; hepatocellular carcinoma; HSF1; signaling pathways |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:16 |
| Last Modified: | 28 Feb 2019 06:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1437 |
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