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Article: Endoplasmic reticulum-localized ECM1b suppresses tumor growth and regulates MYC and MTORC1 through modulating MTORC2 activation in esophageal squamous cell carcinoma

TitleEndoplasmic reticulum-localized ECM1b suppresses tumor growth and regulates MYC and MTORC1 through modulating MTORC2 activation in esophageal squamous cell carcinoma
Authors
KeywordsSignal transduction
Protein translation
Esophageal cancer
Issue Date2019
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet
Citation
Cancer Letters, 2019, v. 461, p. 56-64 How to Cite?
AbstractEsophageal squamous cell carcinoma (ESCC) is a deadly disease with dismal 5-year survival. Extracellular matrix protein 1 (ECMI) was identified as one of the most downregulated genes by transcriptomic analysis of normal esophageal/ESCC paired tissue samples. ECMI plays oncogenic roles in cancer development in various cancer types. However, little is known about its role in ESCC. In vivo and in vitro functional assays coupled with analyses on public datasets and detailed molecular and mechanistic analyses were used to study the gene. We demonstrate that as opposed to the previously identified oncogenic role of ECM1a, ECM1b is a novel tumor suppressor in ESCC. ECM1 is significantly downregulated in ESCC and several other squamous cell carcinomas. ECM1b encodes a cellular protein that suppresses MYC protein expression and MTORC1 signaling activity. MTORC2 inactivation leads to suppressed MYC expression and MTORC1 signaling. ECM1b localizes to the endoplasmic reticulum and suppresses MTORC2 activation by inhibiting MTORC2/ribosome association. By regulating MTORC2/MYC/MTORC1 signaling, ECM1b suppresses general protein translation and enhances chemosensitivity. We provide evidence establishing a novel role of ECM1 in cancer that suggests ECM1b as a biomarker for ESCC disease management.
Persistent Identifierhttp://hdl.handle.net/10722/273855
ISSN
2017 Impact Factor: 6.491
2015 SCImago Journal Rankings: 2.331
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYu, Z-
dc.contributor.authorKo, JMY-
dc.contributor.authorNing, L-
dc.contributor.authorDai, W-
dc.contributor.authorLaw, SYK-
dc.contributor.authorLung, ML-
dc.date.accessioned2019-08-18T14:49:57Z-
dc.date.available2019-08-18T14:49:57Z-
dc.date.issued2019-
dc.identifier.citationCancer Letters, 2019, v. 461, p. 56-64-
dc.identifier.issn0304-3835-
dc.identifier.urihttp://hdl.handle.net/10722/273855-
dc.description.abstractEsophageal squamous cell carcinoma (ESCC) is a deadly disease with dismal 5-year survival. Extracellular matrix protein 1 (ECMI) was identified as one of the most downregulated genes by transcriptomic analysis of normal esophageal/ESCC paired tissue samples. ECMI plays oncogenic roles in cancer development in various cancer types. However, little is known about its role in ESCC. In vivo and in vitro functional assays coupled with analyses on public datasets and detailed molecular and mechanistic analyses were used to study the gene. We demonstrate that as opposed to the previously identified oncogenic role of ECM1a, ECM1b is a novel tumor suppressor in ESCC. ECM1 is significantly downregulated in ESCC and several other squamous cell carcinomas. ECM1b encodes a cellular protein that suppresses MYC protein expression and MTORC1 signaling activity. MTORC2 inactivation leads to suppressed MYC expression and MTORC1 signaling. ECM1b localizes to the endoplasmic reticulum and suppresses MTORC2 activation by inhibiting MTORC2/ribosome association. By regulating MTORC2/MYC/MTORC1 signaling, ECM1b suppresses general protein translation and enhances chemosensitivity. We provide evidence establishing a novel role of ECM1 in cancer that suggests ECM1b as a biomarker for ESCC disease management.-
dc.languageeng-
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet-
dc.relation.ispartofCancer Letters-
dc.subjectSignal transduction-
dc.subjectProtein translation-
dc.subjectEsophageal cancer-
dc.titleEndoplasmic reticulum-localized ECM1b suppresses tumor growth and regulates MYC and MTORC1 through modulating MTORC2 activation in esophageal squamous cell carcinoma-
dc.typeArticle-
dc.identifier.emailYu, Z: zvyu@hku.hk-
dc.identifier.emailKo, JMY: joko@hku.hk-
dc.identifier.emailNing, L: lvwen@hku.hk-
dc.identifier.emailDai, W: weidai2@hku.hk-
dc.identifier.emailLaw, SYK: slaw@hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.authorityKo, JMY=rp02011-
dc.identifier.authorityDai, W=rp02146-
dc.identifier.authorityLaw, SYK=rp00437-
dc.identifier.authorityLung, ML=rp00300-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.canlet.2019.07.005-
dc.identifier.pmid31319137-
dc.identifier.scopuseid_2-s2.0-85068995148-
dc.identifier.hkuros301003-
dc.identifier.hkuros302811-
dc.identifier.volume461-
dc.identifier.spage56-
dc.identifier.epage64-
dc.identifier.isiWOS:000482520900006-
dc.publisher.placeIreland-

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