USP32 confers cancer cell resistance to YM155 via promoting ER-associated degradation of solute carrier protein SLC35F2
DC Field | Value | Language |
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dc.contributor.author | Chandrasekaran, Arun Pandian | - |
dc.contributor.author | Kaushal, Kamini | - |
dc.contributor.author | Park, Chang-Hwan | - |
dc.contributor.author | Kim, Kye-Seong | - |
dc.contributor.author | Ramakrishna, Suresh | - |
dc.date.accessioned | 2022-07-06T12:12:53Z | - |
dc.date.available | 2022-07-06T12:12:53Z | - |
dc.date.created | 2021-12-08 | - |
dc.date.issued | 2021-09 | - |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/140968 | - |
dc.description.abstract | Background: The most commonly preferred chemotherapeutic agents to treat cancers are small-molecule drugs. However, the differential sensitivity of various cancer cells to small molecules and untargeted delivery narrow the range of potential therapeutic applications. The mechanisms responsible for drug resistance in a variety of cancer cells are also largely unknown. Several deubiquitinating enzymes (DUBs) are the main determinants of drug resistance in cancer cells. Methods: We used CRISPR-Cas9 to perform genome-scale knockout of the entire set of genes encoding ubiquitin-specific proteases (USPs) and systematically screened for DUBs resistant to the clinically evaluated anticancer compound YM155. A series of in vitro and in vivo experiments were conducted to reveal the relationship between USP32 and SLC35F2 on YM155-mediated DNA damage in cancer cells. Results: CRISPR-based dual-screening method identified USP32 as a novel DUB that governs resistance for uptake of YM155 by destabilizing protein levels of SLC35F2, a solute-carrier protein essential for the uptake of YM155. The expression of USP32 and SLC35F2 was negatively correlated across a panel of tested cancer cell lines. YM155-resistant cancer cells in particular exhibited elevated expression of USP32 and low expression of SLC35F2. Conclusion: Collectively, our DUB-screening strategy revealed a resistance mechanism governed by USP32 associated with YM155 resistance in breast cancers, one that presents an attractive molecular target for anti-cancer therapies. Targeted genome knockout verified that USP32 is the main determinant of SLC35F2 protein stability in vitro and in vivo, suggesting a novel way to treat tumors resistant to small-molecule drugs. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | Ivyspring International Publisher | - |
dc.title | USP32 confers cancer cell resistance to YM155 via promoting ER-associated degradation of solute carrier protein SLC35F2 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Park, Chang-Hwan | - |
dc.contributor.affiliatedAuthor | Kim, Kye-Seong | - |
dc.contributor.affiliatedAuthor | Ramakrishna, Suresh | - |
dc.identifier.doi | 10.7150/THNO.63806 | - |
dc.identifier.scopusid | 2-s2.0-85117231076 | - |
dc.identifier.wosid | 000719160500003 | - |
dc.identifier.bibliographicCitation | Theranostics, v.11, no.20, pp.9752 - 9771 | - |
dc.relation.isPartOf | Theranostics | - |
dc.citation.title | Theranostics | - |
dc.citation.volume | 11 | - |
dc.citation.number | 20 | - |
dc.citation.startPage | 9752 | - |
dc.citation.endPage | 9771 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | PROTEASOME INHIBITORS | - |
dc.subject.keywordPlus | SURVIVIN | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | UBIQUITINATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | CARCINOMA | - |
dc.subject.keywordPlus | DEATH | - |
dc.subject.keywordPlus | PROGRESSION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordAuthor | Cell apoptosis | - |
dc.subject.keywordAuthor | DNA damage | - |
dc.subject.keywordAuthor | Dose response | - |
dc.subject.keywordAuthor | Drug transport-cargo | - |
dc.subject.keywordAuthor | Human tumor tissues | - |
dc.identifier.url | https://www.thno.org/v11p9752.htm | - |
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