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Article: TPI1-reduced extracellular vesicles mediated by Rab20 downregulation promotes aerobic glycolysis to drive hepatocarcinogenesis

TitleTPI1-reduced extracellular vesicles mediated by Rab20 downregulation promotes aerobic glycolysis to drive hepatocarcinogenesis
Authors
KeywordsExtracellular vesicles
Glycolysis
Hepatocellular carcinoma
Rab20 GTPase
Triosephosphate isomerase 1
Issue Date2021
PublisherWiley on behalf of the International Society for Extracellular Vesicles.
Citation
Journal of Extracellular Vesicles, 2021, v. 10 n. 10, article no. e12135 How to Cite?
AbstractRab GTPases are major mediators that ensure the proper spatiotemporal regulation of intracellular trafficking. Functional impairment and altered expression of Rab proteins have been revealed in various human cancers. There is an emerging evidence about the role of Rab proteins in the biogenesis of extracellular vesicles (EVs). In hepatocellular carcinoma (HCC), using RNA sequencing comparing expression profiles of adjacent non-tumorous tissues and HCC, Rab20 is identified to be the most frequently downregulated Rab member in HCC. Functionally, restoration of Rab20 in metastatic HCC cells results in the release of EVs with a diminished activity to promote cell growth, motility and metastasis. Conversely, EVs released from normal liver cells with Rab20 knockdown loses suppressive effect on HCC cell growth and motility. Proteomic profiling revealed the level of triosephosphate isomerase 1 (TPI1), a glycolytic enzyme, in EVs to be positively associated with Rab20 expression of the releasing cells. TPI1 targeted to be expressed in EVs released by Rab20 knockdown cells compromises the oncogenic activity of EVs. Besides, EVs released by TPI1 knockdown cells recapitulates the promoting effect of EVs derived from HCC cells with Rab20 underexpression. Aerobic glycolysis is beneficial to the survival and proliferation of tumour cells. Here, we observed that the enhanced cell growth and motility are driven by the enhanced aerobic glycolysis induced by EVs with reduced TPI1. The addition of glycolytic inhibitor blocks the promoting effect of EVs with reduced TPI1. Taken together, our study provides a mechanistic link among tumour cell-derived EVs and glucose metabolism in HCC with Rab20 deregulation.
Persistent Identifierhttp://hdl.handle.net/10722/301935
ISSN
2023 Impact Factor: 15.5
2023 SCImago Journal Rankings: 4.268
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, BHM-
dc.contributor.authorTey, SK-
dc.contributor.authorMao, X-
dc.contributor.authorMa, APY-
dc.contributor.authorYeung, CLS-
dc.contributor.authorWong, SWK-
dc.contributor.authorNg, TH-
dc.contributor.authorXu, Y-
dc.contributor.authorYao, Y-
dc.contributor.authorFung, EYM-
dc.contributor.authorTan, KV-
dc.contributor.authorKhong, PL-
dc.contributor.authorHo, DWH-
dc.contributor.authorNg, IOL-
dc.contributor.authorTang, AHN-
dc.contributor.authorCai, SH-
dc.contributor.authorYun, JP-
dc.contributor.authorYam, JWP-
dc.date.accessioned2021-08-21T03:29:09Z-
dc.date.available2021-08-21T03:29:09Z-
dc.date.issued2021-
dc.identifier.citationJournal of Extracellular Vesicles, 2021, v. 10 n. 10, article no. e12135-
dc.identifier.issn2001-3078-
dc.identifier.urihttp://hdl.handle.net/10722/301935-
dc.description.abstractRab GTPases are major mediators that ensure the proper spatiotemporal regulation of intracellular trafficking. Functional impairment and altered expression of Rab proteins have been revealed in various human cancers. There is an emerging evidence about the role of Rab proteins in the biogenesis of extracellular vesicles (EVs). In hepatocellular carcinoma (HCC), using RNA sequencing comparing expression profiles of adjacent non-tumorous tissues and HCC, Rab20 is identified to be the most frequently downregulated Rab member in HCC. Functionally, restoration of Rab20 in metastatic HCC cells results in the release of EVs with a diminished activity to promote cell growth, motility and metastasis. Conversely, EVs released from normal liver cells with Rab20 knockdown loses suppressive effect on HCC cell growth and motility. Proteomic profiling revealed the level of triosephosphate isomerase 1 (TPI1), a glycolytic enzyme, in EVs to be positively associated with Rab20 expression of the releasing cells. TPI1 targeted to be expressed in EVs released by Rab20 knockdown cells compromises the oncogenic activity of EVs. Besides, EVs released by TPI1 knockdown cells recapitulates the promoting effect of EVs derived from HCC cells with Rab20 underexpression. Aerobic glycolysis is beneficial to the survival and proliferation of tumour cells. Here, we observed that the enhanced cell growth and motility are driven by the enhanced aerobic glycolysis induced by EVs with reduced TPI1. The addition of glycolytic inhibitor blocks the promoting effect of EVs with reduced TPI1. Taken together, our study provides a mechanistic link among tumour cell-derived EVs and glucose metabolism in HCC with Rab20 deregulation.-
dc.languageeng-
dc.publisherWiley on behalf of the International Society for Extracellular Vesicles.-
dc.relation.ispartofJournal of Extracellular Vesicles-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectExtracellular vesicles-
dc.subjectGlycolysis-
dc.subjectHepatocellular carcinoma-
dc.subjectRab20 GTPase-
dc.subjectTriosephosphate isomerase 1-
dc.titleTPI1-reduced extracellular vesicles mediated by Rab20 downregulation promotes aerobic glycolysis to drive hepatocarcinogenesis-
dc.typeArticle-
dc.identifier.emailTey, SK: szekeong@hku.hk-
dc.identifier.emailMao, X: susanmao@hku.hk-
dc.identifier.emailNg, TH: tonyng93@hku.hk-
dc.identifier.emailXu, Y: xuyihrb@hku.hk-
dc.identifier.emailYao, Y: yaoyue@hku.hk-
dc.identifier.emailFung, EYM: eva.fungym@hku.hk-
dc.identifier.emailTan, KV: kvtan@hku.hk-
dc.identifier.emailHo, DWH: dwhho@hku.hk-
dc.identifier.emailNg, IOL: iolng@hku.hk-
dc.identifier.emailTang, AHN: alextang@pathology.hku.hk-
dc.identifier.emailYam, JWP: judyyam@pathology.hku.hk-
dc.identifier.authorityMao, X=rp02828-
dc.identifier.authorityFung, EYM=rp01986-
dc.identifier.authorityKhong, PL=rp00467-
dc.identifier.authorityHo, DWH=rp02285-
dc.identifier.authorityNg, IOL=rp00335-
dc.identifier.authorityTang, AHN=rp02468-
dc.identifier.authorityYam, JWP=rp00468-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1002/jev2.12135-
dc.identifier.pmid34401050-
dc.identifier.pmcidPMC8357635-
dc.identifier.scopuseid_2-s2.0-85113143588-
dc.identifier.hkuros324189-
dc.identifier.volume10-
dc.identifier.issue10-
dc.identifier.spagearticle no. e12135-
dc.identifier.epagearticle no. e12135-
dc.identifier.isiWOS:000684003500001-
dc.publisher.placeUnited Kingdom-

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