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Article: Ascites-derived ALDH+CD44+ tumour cell subsets endow stemness, metastasis and metabolic switch via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling in ovarian cancer

TitleAscites-derived ALDH+CD44+ tumour cell subsets endow stemness, metastasis and metabolic switch via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling in ovarian cancer
Authors
Keywordsanimal experiment
animal model
ascites
cancer prognosis
cancer stem cell
Issue Date2020
PublisherSpringer Nature, published in association with Cancer Research UK. The Journal's web site is located at http://www.nature.com/bjc
Citation
British Journal of Cancer, 2020, v. 123, p. 275-287 How to Cite?
AbstractBackground: Ovarian cancer is characterised by frequent recurrence due to persistent presence of residual cancer stem cells (CSCs). Here, we identify and characterise tumour subsets from ascites-derived tumour cells with stemness, metastasis and metabolic switch properties and to delineate the involvement of pyruvate dehydrogenase kinase 4 (PDK4) in such process. Methods: Ovarian cancer cells/cell lines derived from ascites were used for tumourspheres/ALDH+CD44+ subset isolation. The functional roles and downstream signalling of PDK4 were explored. Its association with clinical outcome of ovarian cancer was analysed. Results: We demonstrated enhanced CSC characteristics of tumour cells derived from ovarian cancer ascites, concomitant with ALDH and CD44 subset enrichment and high PDK4 expression, compared to primary tumours. We further showed tumourspheres/ALDH+CD44+ subsets from ascites-derived tumour cells/cell lines with CSC properties and enhanced glycolysis. Clinically, PDK4 expression was correlated with aggressive features. Notably, blockade of PDK4 in tumourspheres/ALDH+CD44+ subsets led to inhibition of CSC characteristics, glycolysis and activation of STAT3/AKT/NF-κB/IL-8 (signal transducer and activator of transcription 3/protein kinases B/nuclear factor-κB/interleukin-8) signalling. Conversely, overexpression of PDK4 in ALDH−CD44– subsets exerted the opposite effects. Conclusion: Ascites-derived ALDH+CD44+ tumour cell subsets endow stemness, metastatic and metabolic switch properties via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling, suggesting PDK4 as a viable therapeutic molecular target for ovarian cancer management.
Persistent Identifierhttp://hdl.handle.net/10722/289845
ISSN
2020 Impact Factor: 7.64
2020 SCImago Journal Rankings: 2.833
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJIANG, XY-
dc.contributor.authorSiu, MKY-
dc.contributor.authorWANG, JJ-
dc.contributor.authorMO, XT-
dc.contributor.authorLeung, THY-
dc.contributor.authorChan, DW-
dc.contributor.authorCheung, ANY-
dc.contributor.authorNgan, HYS-
dc.contributor.authorChan, KKL-
dc.date.accessioned2020-10-22T08:18:17Z-
dc.date.available2020-10-22T08:18:17Z-
dc.date.issued2020-
dc.identifier.citationBritish Journal of Cancer, 2020, v. 123, p. 275-287-
dc.identifier.issn0007-0920-
dc.identifier.urihttp://hdl.handle.net/10722/289845-
dc.description.abstractBackground: Ovarian cancer is characterised by frequent recurrence due to persistent presence of residual cancer stem cells (CSCs). Here, we identify and characterise tumour subsets from ascites-derived tumour cells with stemness, metastasis and metabolic switch properties and to delineate the involvement of pyruvate dehydrogenase kinase 4 (PDK4) in such process. Methods: Ovarian cancer cells/cell lines derived from ascites were used for tumourspheres/ALDH+CD44+ subset isolation. The functional roles and downstream signalling of PDK4 were explored. Its association with clinical outcome of ovarian cancer was analysed. Results: We demonstrated enhanced CSC characteristics of tumour cells derived from ovarian cancer ascites, concomitant with ALDH and CD44 subset enrichment and high PDK4 expression, compared to primary tumours. We further showed tumourspheres/ALDH+CD44+ subsets from ascites-derived tumour cells/cell lines with CSC properties and enhanced glycolysis. Clinically, PDK4 expression was correlated with aggressive features. Notably, blockade of PDK4 in tumourspheres/ALDH+CD44+ subsets led to inhibition of CSC characteristics, glycolysis and activation of STAT3/AKT/NF-κB/IL-8 (signal transducer and activator of transcription 3/protein kinases B/nuclear factor-κB/interleukin-8) signalling. Conversely, overexpression of PDK4 in ALDH−CD44– subsets exerted the opposite effects. Conclusion: Ascites-derived ALDH+CD44+ tumour cell subsets endow stemness, metastatic and metabolic switch properties via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling, suggesting PDK4 as a viable therapeutic molecular target for ovarian cancer management.-
dc.languageeng-
dc.publisherSpringer Nature, published in association with Cancer Research UK. The Journal's web site is located at http://www.nature.com/bjc-
dc.relation.ispartofBritish Journal of Cancer-
dc.subjectanimal experiment-
dc.subjectanimal model-
dc.subjectascites-
dc.subjectcancer prognosis-
dc.subjectcancer stem cell-
dc.titleAscites-derived ALDH+CD44+ tumour cell subsets endow stemness, metastasis and metabolic switch via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling in ovarian cancer-
dc.typeArticle-
dc.identifier.emailSiu, MKY: mkysiu@hku.hk-
dc.identifier.emailChan, DW: dwchan@hku.hk-
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hk-
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hk-
dc.identifier.emailChan, KKL: kklchan@hkucc.hku.hk-
dc.identifier.authoritySiu, MKY=rp00275-
dc.identifier.authorityChan, DW=rp00543-
dc.identifier.authorityCheung, ANY=rp00542-
dc.identifier.authorityNgan, HYS=rp00346-
dc.identifier.authorityChan, KKL=rp00499-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/s41416-020-0865-z-
dc.identifier.pmid32390009-
dc.identifier.pmcidPMC7374705-
dc.identifier.scopuseid_2-s2.0-85084367807-
dc.identifier.hkuros316305-
dc.identifier.volume123-
dc.identifier.spage275-
dc.identifier.epage287-
dc.identifier.isiWOS:000531456900006-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl0007-0920-

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