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Article: Clathrin light chain A facilitates small extracellular vesicle uptake to promote hepatocellular carcinoma progression.

TitleClathrin light chain A facilitates small extracellular vesicle uptake to promote hepatocellular carcinoma progression.
Authors
KeywordsBiomarkers
Capping actin protein gelsolin-like
Clathrin light chain A
Endocytosis
Hepatocellular carcinoma
Patient-derived xenografts
Pitstop 2
Small extracellular vesicles
Issue Date24-Jun-2023
PublisherSpringer
Citation
Hepatology International, 2023 How to Cite?
AbstractBACKGROUND\nMATERIALS AND METHODS\nRESULTS\nCONCLUSIONS\nEndocytosis is a fundamental process for internalizing small extracellular vesicles (sEVs). The present study aimed to elucidate the role of clathrin light chain A (CLTA) in sEV uptake in hepatocellular carcinoma (HCC).\nCLTA expression was analyzed by bioinformatics, quantitative PCR and immunohistochemistry. The clinical relevance of CLTA was analyzed by Fisher's exact test, Kaplan-Meier analysis, and multivariate cox regression model. The functions of CLTA in sEV uptake and cancerous properties were examined by PKH67-sEV uptake, MTT, colony formation, and transwell assays. Mass spectrometry was used to identify the downstream effectors of CLTA. CLTA inhibitor, Pitstop 2, was tested in a mouse model of patient-derived xenografts (PDXs).\nCLTA expression was higher in tumor tissues than in non-tumorous liver tissues and progressively increased from the early to late tumor stage. CLTA overexpression was associated with larger tumor size and poor prognosis in HCC. Cellular CLTA contributed to the sEV uptake, resulting in enhanced cancerous properties. Mechanistically, CLTA increases capping actin protein gelsolin-like (CAPG) expression to facilitate sEV uptake, thereby promoting the proliferation, motility, and invasiveness of HCC cells. What's more, the CLTA inhibitor Pitstop 2 alone or in combination with sorafenib attenuated tumor growth in mice implanted with PDXs.\nThe study reveals the role of CLTA in sEV uptake to promote HCC progression. Inhibition of CLTA and its mediated pathway illuminate a new therapeutic strategy for HCC patients.
Persistent Identifierhttp://hdl.handle.net/10722/331267
ISSN
2023 Impact Factor: 5.9
2023 SCImago Journal Rankings: 1.813
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorXu, Y-
dc.contributor.authorYao, Y-
dc.contributor.authorYu, L-
dc.contributor.authorFung, HL-
dc.contributor.authorTang, AHN-
dc.contributor.authorNg, IO-
dc.contributor.authorWong, MYM-
dc.contributor.authorChe, CM-
dc.contributor.authorYun, JP-
dc.contributor.authorCui, Y-
dc.contributor.authorYam, JWP-
dc.date.accessioned2023-09-21T06:54:11Z-
dc.date.available2023-09-21T06:54:11Z-
dc.date.issued2023-06-24-
dc.identifier.citationHepatology International, 2023-
dc.identifier.issn1936-0533-
dc.identifier.urihttp://hdl.handle.net/10722/331267-
dc.description.abstractBACKGROUND\nMATERIALS AND METHODS\nRESULTS\nCONCLUSIONS\nEndocytosis is a fundamental process for internalizing small extracellular vesicles (sEVs). The present study aimed to elucidate the role of clathrin light chain A (CLTA) in sEV uptake in hepatocellular carcinoma (HCC).\nCLTA expression was analyzed by bioinformatics, quantitative PCR and immunohistochemistry. The clinical relevance of CLTA was analyzed by Fisher's exact test, Kaplan-Meier analysis, and multivariate cox regression model. The functions of CLTA in sEV uptake and cancerous properties were examined by PKH67-sEV uptake, MTT, colony formation, and transwell assays. Mass spectrometry was used to identify the downstream effectors of CLTA. CLTA inhibitor, Pitstop 2, was tested in a mouse model of patient-derived xenografts (PDXs).\nCLTA expression was higher in tumor tissues than in non-tumorous liver tissues and progressively increased from the early to late tumor stage. CLTA overexpression was associated with larger tumor size and poor prognosis in HCC. Cellular CLTA contributed to the sEV uptake, resulting in enhanced cancerous properties. Mechanistically, CLTA increases capping actin protein gelsolin-like (CAPG) expression to facilitate sEV uptake, thereby promoting the proliferation, motility, and invasiveness of HCC cells. What's more, the CLTA inhibitor Pitstop 2 alone or in combination with sorafenib attenuated tumor growth in mice implanted with PDXs.\nThe study reveals the role of CLTA in sEV uptake to promote HCC progression. Inhibition of CLTA and its mediated pathway illuminate a new therapeutic strategy for HCC patients.-
dc.languageeng-
dc.publisherSpringer-
dc.relation.ispartofHepatology International-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectBiomarkers-
dc.subjectCapping actin protein gelsolin-like-
dc.subjectClathrin light chain A-
dc.subjectEndocytosis-
dc.subjectHepatocellular carcinoma-
dc.subjectPatient-derived xenografts-
dc.subjectPitstop 2-
dc.subjectSmall extracellular vesicles-
dc.titleClathrin light chain A facilitates small extracellular vesicle uptake to promote hepatocellular carcinoma progression.-
dc.typeArticle-
dc.identifier.doi10.1007/s12072-023-10562-5-
dc.identifier.pmid37354358-
dc.identifier.scopuseid_2-s2.0-85163203531-
dc.identifier.eissn1936-0541-
dc.identifier.isiWOS:001016175900001-
dc.identifier.issnl1936-0533-

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