File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Heat shock factor 1 epigenetically stimulates glutaminase-1-dependent mTOR activation to promote colorectal carcinogenesis

TitleHeat shock factor 1 epigenetically stimulates glutaminase-1-dependent mTOR activation to promote colorectal carcinogenesis
Authors
Keywordscolorectal cancer
HSF1
glutamine metabolism
GLS1
MIR137HG
Issue Date2018
PublisherCell Press. The Journal's web site is located at https://www.cell.com/molecular-therapy-family/home
Citation
Molecular Therapy, 2018, v. 26 n. 7, p. 1828-1839 How to Cite?
AbstractHeat shock factor 1 (HSF1) generally exhibits its properties under stress conditions. In tumors, HSF1 has a pleiotropic feature in regulating growth, survival, and aggressiveness of cancer cells. In this study, we found HSF1 was increased in colorectal cancer (CRC) and had a positive correlation with shorter disease-free survival (DFS). Knockdown of HSF1 in CRC cells attenuated their growth while inhibiting mTOR activation and glutamine metabolism. HSF1 inhibited the expression of microRNA137 (MIR137), which targeted GLS1 (glutaminase 1), thus stimulating GLS1 protein expression to promote glutaminolysis and mTOR activation. HSF1 bound DNA methyltransferase DNMT3a and recruited it to the promoter of lncRNA MIR137 host gene (MIR137HG), suppressing the generation of primary MIR137. The chemical inhibitor of HSF1 also reduced cell growth, increased apoptosis, and impaired glutamine metabolism in vitro. Moreover, both chemical inhibition and genetic knockout of HSF1 succeeded in increasing MIR137 expression, reducing GLS1 expression, and alleviating colorectal tumorigenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS) mice. In conclusion, HSF1 expression was increased and associated with poor prognosis in CRC. By recruiting DNMT3a to suppress the expression of MIR137 that targets GLS1 mRNA, HSF1 stimulated GLS1-dependent mTOR activation to promote colorectal carcinogenesis. Therefore, targeting HSF1 to attenuate glutaminolysis and mTOR activation could be a promising approach for CRC treatment.
DescriptionHybrid open access
Persistent Identifierhttp://hdl.handle.net/10722/301135
ISSN
2023 Impact Factor: 12.1
2023 SCImago Journal Rankings: 3.736
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, J-
dc.contributor.authorSong, P-
dc.contributor.authorJiang, T-
dc.contributor.authorDai, D-
dc.contributor.authorWang, H-
dc.contributor.authorSun, J-
dc.contributor.authorZhu, L-
dc.contributor.authorXu, W-
dc.contributor.authorFeng, L-
dc.contributor.authorShin, VY-
dc.contributor.authorMorrison, H-
dc.contributor.authorWang, X-
dc.contributor.authorJin, H-
dc.date.accessioned2021-07-27T08:06:38Z-
dc.date.available2021-07-27T08:06:38Z-
dc.date.issued2018-
dc.identifier.citationMolecular Therapy, 2018, v. 26 n. 7, p. 1828-1839-
dc.identifier.issn1525-0016-
dc.identifier.urihttp://hdl.handle.net/10722/301135-
dc.descriptionHybrid open access-
dc.description.abstractHeat shock factor 1 (HSF1) generally exhibits its properties under stress conditions. In tumors, HSF1 has a pleiotropic feature in regulating growth, survival, and aggressiveness of cancer cells. In this study, we found HSF1 was increased in colorectal cancer (CRC) and had a positive correlation with shorter disease-free survival (DFS). Knockdown of HSF1 in CRC cells attenuated their growth while inhibiting mTOR activation and glutamine metabolism. HSF1 inhibited the expression of microRNA137 (MIR137), which targeted GLS1 (glutaminase 1), thus stimulating GLS1 protein expression to promote glutaminolysis and mTOR activation. HSF1 bound DNA methyltransferase DNMT3a and recruited it to the promoter of lncRNA MIR137 host gene (MIR137HG), suppressing the generation of primary MIR137. The chemical inhibitor of HSF1 also reduced cell growth, increased apoptosis, and impaired glutamine metabolism in vitro. Moreover, both chemical inhibition and genetic knockout of HSF1 succeeded in increasing MIR137 expression, reducing GLS1 expression, and alleviating colorectal tumorigenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS) mice. In conclusion, HSF1 expression was increased and associated with poor prognosis in CRC. By recruiting DNMT3a to suppress the expression of MIR137 that targets GLS1 mRNA, HSF1 stimulated GLS1-dependent mTOR activation to promote colorectal carcinogenesis. Therefore, targeting HSF1 to attenuate glutaminolysis and mTOR activation could be a promising approach for CRC treatment.-
dc.languageeng-
dc.publisherCell Press. The Journal's web site is located at https://www.cell.com/molecular-therapy-family/home-
dc.relation.ispartofMolecular Therapy-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectcolorectal cancer-
dc.subjectHSF1-
dc.subjectglutamine metabolism-
dc.subjectGLS1-
dc.subjectMIR137HG-
dc.titleHeat shock factor 1 epigenetically stimulates glutaminase-1-dependent mTOR activation to promote colorectal carcinogenesis-
dc.typeArticle-
dc.identifier.emailShin, VY: vyshin@hku.hk-
dc.identifier.authorityShin, VY=rp02000-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.ymthe.2018.04.014-
dc.identifier.pmid29730197-
dc.identifier.pmcidPMC6035735-
dc.identifier.scopuseid_2-s2.0-85046795170-
dc.identifier.hkuros323790-
dc.identifier.volume26-
dc.identifier.issue7-
dc.identifier.spage1828-
dc.identifier.epage1839-
dc.identifier.isiWOS:000439688600021-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats