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Article: Gain-of-function hot spot mutant p53R248Q regulation of integrin/FAK/ERK signaling in esophageal squamous cell carcinoma

TitleGain-of-function hot spot mutant p53R248Q regulation of integrin/FAK/ERK signaling in esophageal squamous cell carcinoma
Authors
KeywordsSignal transduction
Extracellular matrix
Esophageal cancer
Issue Date2021
PublisherElsevier: Creative Commons Attribution Non-Commercial No-Derivatives License. The Journal's web site is located at http://www.transonc.com
Citation
Translational Oncology, 2021, v. 14 n. 1, p. article no. 100982 How to Cite?
AbstractPurpose: TP53, encoding the protein p53, is among the most frequently mutated genes in all cancers. A high frequency of 60 – 90% mutations is seen in esophageal squamous cell carcinoma (ESCC) patients. Certain p53 mutants show gain-of-function (GoF) oncogenic features unrelated to its wild type functions. Methods: This study functionally characterized a panel of p53 mutants in individual ESCC cell lines and assayed for GoF oncogenic properties. Results: The ESCC cell line with endogenous p53 R248Q expression showed suppressed tumor growth in an immunocompromised mouse model and suppressed colony growth in in vitro three-dimensional culture, when depleted of the endogenous p53 protein expression. This suppression is accompanied by suppressed cell cycle progression, along with reduced integrin expression and decreased focal adhesion kinase and extracellular-regulated protein kinase signaling and can be compensated by expression of a constitutively active mitogen-activated protein. P53 R248Q enhances cell proliferation upon glutamine deprivation, as compared to other non-GoF mutants. Conclusions: In summary, study of the functional contributions of endogenous p53 mutants identified a novel GoF mechanism through which a specific p53 mutant exerts oncogenic features and contributes to ESCC tumorigenesis.
Persistent Identifierhttp://hdl.handle.net/10722/301385
ISSN
2015 Impact Factor: 3.077
2023 SCImago Journal Rankings: 1.263
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYu, VZ-
dc.contributor.authorSO, SS-
dc.contributor.authorLung, ML-
dc.date.accessioned2021-07-27T08:10:16Z-
dc.date.available2021-07-27T08:10:16Z-
dc.date.issued2021-
dc.identifier.citationTranslational Oncology, 2021, v. 14 n. 1, p. article no. 100982-
dc.identifier.issn1944-7124-
dc.identifier.urihttp://hdl.handle.net/10722/301385-
dc.description.abstractPurpose: TP53, encoding the protein p53, is among the most frequently mutated genes in all cancers. A high frequency of 60 – 90% mutations is seen in esophageal squamous cell carcinoma (ESCC) patients. Certain p53 mutants show gain-of-function (GoF) oncogenic features unrelated to its wild type functions. Methods: This study functionally characterized a panel of p53 mutants in individual ESCC cell lines and assayed for GoF oncogenic properties. Results: The ESCC cell line with endogenous p53 R248Q expression showed suppressed tumor growth in an immunocompromised mouse model and suppressed colony growth in in vitro three-dimensional culture, when depleted of the endogenous p53 protein expression. This suppression is accompanied by suppressed cell cycle progression, along with reduced integrin expression and decreased focal adhesion kinase and extracellular-regulated protein kinase signaling and can be compensated by expression of a constitutively active mitogen-activated protein. P53 R248Q enhances cell proliferation upon glutamine deprivation, as compared to other non-GoF mutants. Conclusions: In summary, study of the functional contributions of endogenous p53 mutants identified a novel GoF mechanism through which a specific p53 mutant exerts oncogenic features and contributes to ESCC tumorigenesis.-
dc.languageeng-
dc.publisherElsevier: Creative Commons Attribution Non-Commercial No-Derivatives License. The Journal's web site is located at http://www.transonc.com-
dc.relation.ispartofTranslational Oncology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectSignal transduction-
dc.subjectExtracellular matrix-
dc.subjectEsophageal cancer-
dc.titleGain-of-function hot spot mutant p53R248Q regulation of integrin/FAK/ERK signaling in esophageal squamous cell carcinoma-
dc.typeArticle-
dc.identifier.emailYu, VZ: zvyu@hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.authorityYu, VZ=rp02756-
dc.identifier.authorityLung, ML=rp00300-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.tranon.2020.100982-
dc.identifier.pmid33395748-
dc.identifier.pmcidPMC7744772-
dc.identifier.scopuseid_2-s2.0-85097467752-
dc.identifier.hkuros323387-
dc.identifier.volume14-
dc.identifier.issue1-
dc.identifier.spagearticle no. 100982-
dc.identifier.epagearticle no. 100982-
dc.identifier.isiWOS:000604582000011-
dc.publisher.placeUnited States-

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