Integrin alpha 6 beta 4-Src-AKT signaling induces cellular senescence by counteracting apoptosis in irradiated tumor cells and tissues
DC Field | Value | Language |
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dc.contributor.author | Jung, Seung Hee | - |
dc.contributor.author | Lee, Minyoung | - |
dc.contributor.author | Park, Hyun A. | - |
dc.contributor.author | Lee, Hyung Chul | - |
dc.contributor.author | Kang, Donghee | - |
dc.contributor.author | Hwang, Hyun Jung | - |
dc.contributor.author | Park, Chanho | - |
dc.contributor.author | Yu, Dong-Min | - |
dc.contributor.author | Jung, Yu Ri | - |
dc.contributor.author | Hong, Mi-Na | - |
dc.contributor.author | Kim, Yong-Nyun | - |
dc.contributor.author | Park, Heon Joo | - |
dc.contributor.author | Ko, Young-Gyu | - |
dc.contributor.author | Lee, Jae-Seon | - |
dc.date.accessioned | 2021-09-01T20:12:53Z | - |
dc.date.available | 2021-09-01T20:12:53Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2019-02 | - |
dc.identifier.issn | 1350-9047 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/67861 | - |
dc.description.abstract | Cellular senescence refers to an irreversible growth arrest that is triggered by various intrinsic and extrinsic stresses. Many recent studies have demonstrated that cellular senescence plays a crucial role in the regression of tumors exposed to ionizing radiation (IR), but the underlying mechanism remains unknown. Here we show that the activation of integrin beta 4 is essential for IR-induced cellular senescence. IR treatment results in the phosphorylation of integrin beta 4 at tyrosine residue 1510, leading to activation of the integrin alpha 6 beta 4-Src-AKT signaling pathway. We further reveal that the IR-induced phosphorylation of integrin beta 4 is regulated by the cholesterol content and membrane fluidity. We also find that IR-induced p53-caspase signaling is independent of integrin alpha 6 beta 4-Src-AKT signaling. Finally, we show that siRNA-or inhibitor-mediated blockade of integrin alpha 6 beta 4-Src-AKT signaling switches the post-irradiation fate from senescence to apoptosis, under p53 activated condition, in both cancer cells and tumor tissues of xenograft mice. On the basis of our finding that, integrin alpha 6 beta 4 is specifically activated and acts primarily to induce premature senescence in irradiated cancer cells, we propose that this integrin may be a valuable target and biomarker for radiotherapy. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | LIPID RAFTS | - |
dc.subject | ACCELERATED SENESCENCE | - |
dc.subject | PREMATURE SENESCENCE | - |
dc.subject | CANCER CELLS | - |
dc.subject | RECEPTOR | - |
dc.subject | RADIATION | - |
dc.subject | PHOSPHORYLATION | - |
dc.subject | ACTIVATION | - |
dc.subject | SURVIVAL | - |
dc.subject | GROWTH | - |
dc.title | Integrin alpha 6 beta 4-Src-AKT signaling induces cellular senescence by counteracting apoptosis in irradiated tumor cells and tissues | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Ko, Young-Gyu | - |
dc.identifier.doi | 10.1038/s41418-018-0114-7 | - |
dc.identifier.scopusid | 2-s2.0-85047180814 | - |
dc.identifier.wosid | 000455715000004 | - |
dc.identifier.bibliographicCitation | CELL DEATH AND DIFFERENTIATION, v.26, no.2, pp.245 - 259 | - |
dc.relation.isPartOf | CELL DEATH AND DIFFERENTIATION | - |
dc.citation.title | CELL DEATH AND DIFFERENTIATION | - |
dc.citation.volume | 26 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 245 | - |
dc.citation.endPage | 259 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | LIPID RAFTS | - |
dc.subject.keywordPlus | ACCELERATED SENESCENCE | - |
dc.subject.keywordPlus | PREMATURE SENESCENCE | - |
dc.subject.keywordPlus | CANCER CELLS | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | RADIATION | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | SURVIVAL | - |
dc.subject.keywordPlus | GROWTH | - |
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