Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/26676
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dc.contributor.authorEichelmann, Ann-Kathrin-
dc.contributor.authorMayne, George C-
dc.contributor.authorChiam, Karen-
dc.contributor.authorDue, Steven L-
dc.contributor.authorBastian, Isabell-
dc.contributor.authorButz, Frederike-
dc.contributor.authorWang, Tingting-
dc.contributor.authorSykes, Pamela J-
dc.contributor.authorClemons, Nicholas J-
dc.contributor.authorLiu, David Shi Hao-
dc.contributor.authorMichael, Michael Z-
dc.contributor.authorKarapetis, Christos S-
dc.contributor.authorHummel, Richard-
dc.contributor.authorWatson, David I-
dc.contributor.authorHussey, Damian J-
dc.date2021-05-24-
dc.date.accessioned2021-06-07T06:03:53Z-
dc.date.available2021-06-07T06:03:53Z-
dc.date.issued2021-05-24-
dc.identifier.citationInternational Journal of Molecular Sciences 2021; 22(11): 5547-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/26676-
dc.description.abstractTP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53.-
dc.language.isoeng-
dc.subjectSLC7A11-
dc.subjectchemoresistance-
dc.subjectmiR-27a-3p-
dc.subjectmiRNA-
dc.subjectoesophageal cancer-
dc.subjectoestrogen receptor modulator-
dc.subjectradioresistance-
dc.subjectreactive oxidative species-
dc.subjectribosome-
dc.subjectxCT-
dc.titleMutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression.-
dc.typeJournal Article-
dc.identifier.journaltitleInternational Journal of Molecular Sciences-
dc.identifier.affiliationDepartment of General, Visceral and Transplant Surgery, University Hospital of Münster, Waldeyerstrasse 1, 48149 Münster, Germanyen
dc.identifier.affiliationPeter MacCallum Cancer Centre, 305 Grattan St, Melbourne, VIC 3000, Australiaen
dc.identifier.affiliationDepartment of Surgery, Flinders Medical Centre, Bedford Park, Adelaide, SA 5042, Australiaen
dc.identifier.affiliationFlinders Health and Medical Research Institute-Cancer Program, Flinders University, Bedford Park, Adelaide, SA 5042, Australiaen
dc.identifier.affiliationSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australiaen
dc.identifier.affiliationSurgeryen
dc.identifier.affiliationDepartment of Gastroenterology, Flinders Medical Centre, Bedford Park, Adelaide, SA 5042, Australiaen
dc.identifier.affiliationDepartment of Medical Oncology, Flinders Medical Centre, Bedford Park, Adelaide, SA 5042, Australiaen
dc.identifier.affiliationDepartment of Surgery, University Hospital of Schleswig-Holstein, Ratzeburger Allee 160, 23538 Lübeck, Germanyen
dc.identifier.doi10.3390/ijms22115547-
dc.identifier.orcid0000-0002-9037-7009-
dc.identifier.orcid0000-0001-8154-6731-
dc.identifier.orcid0000-0002-7739-4787-
dc.identifier.orcid0000-0001-9283-9978-
dc.identifier.orcid0000-0002-7683-2693-
dc.identifier.orcid0000-0002-6121-6740-
dc.identifier.pubmedid34074015-
local.name.researcherLiu, David Shi Hao
item.openairetypeJournal Article-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
item.fulltextNo Fulltext-
item.cerifentitytypePublications-
item.languageiso639-1en-
crisitem.author.deptSurgery-
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