PMID- 29207593
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220321
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 53
DP  - 2017 Oct 31
TI  - Deregulated c-Myc requires a functional HSF1 for experimental and human 
      hepatocarcinogenesis.
PG  - 90638-90650
LID - 10.18632/oncotarget.21469 [doi]
AB  - Deregulated activity of the c-Myc protooncogene is a frequent molecular event 
      underlying mouse and human hepatocarcinogenesis. Nonetheless, the mechanisms 
      sustaining c-Myc oncogenic activity in liver cancer remain scarcely delineated. 
      Recently, we showed that the mammalian target of rapamycin complex 1 (mTORC1) 
      cascade is induced and necessary for c-Myc dependent liver tumor development and 
      progression. Since the heat shock factor 1 (HSF1) transcription factor is a major 
      positive regulator of mTORC1 in the cell, we investigated the functional 
      interaction between HSF1 and c-Myc using in vitro and in vivo approaches. We 
      found that ablation of HSF1 restrains the growth of c-Myc-derived mouse 
      hepatocellular carcinoma (HCC) cell lines, where it induces downregulation of 
      c-Myc levels. Conversely, silencing of c-Myc gene in human and mouse HCC cells 
      led to downregulation of HSF1 expression. Most importantly, overexpression of a 
      dominant negative form of HSF1 (HSF1dn) in the mouse liver via hydrodynamic gene 
      delivery resulted in the complete inhibition of mouse hepatocarcinogenesis driven 
      by overexpression of c-Myc. Altogether, the present results indicate that a 
      functional HSF1 is necessary for c-Myc-driven hepatocarcinogenesis. Consequently, 
      targeting HSF1 might represent a novel and effective therapeutic strategy for the 
      treatment of HCC subsets with activated c-Myc signaling.
FAU - Cigliano, Antonio
AU  - Cigliano A
AD  - Institut fur Pathologie, Universitatsmedizin Greifswald, Greifswald, Germany.
FAU - Pilo, Maria G
AU  - Pilo MG
AD  - Department of Clinical and Experimental Medicine, University of Sassari, Sassari, 
      Italy.
FAU - Li, Lei
AU  - Li L
AD  - School of Pharmacy, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei, China.
FAU - Latte, Gavinella
AU  - Latte G
AD  - Department of Clinical and Experimental Medicine, University of Sassari, Sassari, 
      Italy.
FAU - Szydlowska, Marta
AU  - Szydlowska M
AD  - Institut fur Pathologie, Universitatsmedizin Greifswald, Greifswald, Germany.
FAU - Simile, Maria M
AU  - Simile MM
AD  - Department of Clinical and Experimental Medicine, University of Sassari, Sassari, 
      Italy.
FAU - Paliogiannis, Panagiotis
AU  - Paliogiannis P
AD  - Department of Clinical and Experimental Medicine, University of Sassari, Sassari, 
      Italy.
FAU - Che, Li
AU  - Che L
AD  - Department of Bioengineering and Therapeutic Sciences and Liver Center, 
      University of California, San Francisco, CA, USA.
FAU - Pes, Giovanni M
AU  - Pes GM
AD  - Department of Clinical and Experimental Medicine, University of Sassari, Sassari, 
      Italy.
FAU - Palmieri, Giuseppe
AU  - Palmieri G
AD  - Institute of Biomolecular Chemistry, National Research Council, Sassari, Italy.
FAU - Sini, Maria C
AU  - Sini MC
AD  - Institute of Biomolecular Chemistry, National Research Council, Sassari, Italy.
FAU - Cossu, Antonio
AU  - Cossu A
AD  - Unit of Pathology, Azienda Ospedaliero Universitaria Sassari, Sassari, Italy.
FAU - Porcu, Alberto
AU  - Porcu A
AD  - Department of Clinical and Experimental Medicine, University of Sassari, Sassari, 
      Italy.
FAU - Vidili, Gianpaolo
AU  - Vidili G
AD  - Department of Clinical and Experimental Medicine, University of Sassari, Sassari, 
      Italy.
FAU - Seddaiu, Maria A
AU  - Seddaiu MA
AD  - Department of Clinical and Experimental Medicine, University of Sassari, Sassari, 
      Italy.
FAU - Pascale, Rosa M
AU  - Pascale RM
AD  - Department of Clinical and Experimental Medicine, University of Sassari, Sassari, 
      Italy.
FAU - Ribback, Silvia
AU  - Ribback S
AD  - Institut fur Pathologie, Universitatsmedizin Greifswald, Greifswald, Germany.
FAU - Dombrowski, Frank
AU  - Dombrowski F
AD  - Institut fur Pathologie, Universitatsmedizin Greifswald, Greifswald, Germany.
FAU - Chen, Xin
AU  - Chen X
AD  - Department of Bioengineering and Therapeutic Sciences and Liver Center, 
      University of California, San Francisco, CA, USA.
FAU - Calvisi, Diego F
AU  - Calvisi DF
AD  - Department of Clinical and Experimental Medicine, University of Sassari, Sassari, 
      Italy.
LA  - eng
GR  - P30 DK026743/DK/NIDDK NIH HHS/United States
GR  - R01 CA136606/CA/NCI NIH HHS/United States
GR  - R21 CA198490/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20171003
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5710874
OTO - NOTNLM
OT  - HSF1
OT  - c-Myc
OT  - hepatocellular carcinoma
OT  - liver cancer
OT  - signalling pathways
COIS- CONFLICTS OF INTEREST The authors state the absence of any conflict of interest 
      to disclose.
EDAT- 2017/12/07 06:00
MHDA- 2017/12/07 06:01
PMCR- 2017/10/31
CRDT- 2017/12/07 06:00
PHST- 2017/08/31 00:00 [received]
PHST- 2017/09/21 00:00 [accepted]
PHST- 2017/12/07 06:00 [entrez]
PHST- 2017/12/07 06:00 [pubmed]
PHST- 2017/12/07 06:01 [medline]
PHST- 2017/10/31 00:00 [pmc-release]
AID - 21469 [pii]
AID - 10.18632/oncotarget.21469 [doi]
PST - epublish
SO  - Oncotarget. 2017 Oct 3;8(53):90638-90650. doi: 10.18632/oncotarget.21469. 
      eCollection 2017 Oct 31.