Full metadata record
DC Field | Value | Language |
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dc.citation.number | 1 | - |
dc.citation.startPage | 48 | - |
dc.citation.title | CELL DEATH & DISEASE | - |
dc.citation.volume | 15 | - |
dc.contributor.author | Lee, Dong Min | - |
dc.contributor.author | Kim, In Young | - |
dc.contributor.author | Lee, Hong Jae | - |
dc.contributor.author | Seo, Min Ji | - |
dc.contributor.author | Cho, Mi-Young | - |
dc.contributor.author | Lee, Hae In | - |
dc.contributor.author | Yoon, Gyesoon | - |
dc.contributor.author | Ji, Jae-Hoon | - |
dc.contributor.author | Park, Seok Soon | - |
dc.contributor.author | Jeong, Seong-Yun | - |
dc.contributor.author | Choi, Eun Kyung | - |
dc.contributor.author | Choi, Yong Hyeon | - |
dc.contributor.author | Yun, Chae-Ok | - |
dc.contributor.author | Yeo, Mirae | - |
dc.contributor.author | Kim, Eunhee | - |
dc.contributor.author | Choi, Kyeong Sook | - |
dc.date.accessioned | 2024-01-30T14:05:19Z | - |
dc.date.available | 2024-01-30T14:05:19Z | - |
dc.date.created | 2024-01-15 | - |
dc.date.issued | 2024-01 | - |
dc.description.abstract | Valosin-containing protein (VCP)/p97, an AAA+ ATPase critical for maintaining proteostasis, emerges as a promising target for cancer therapy. This study reveals that targeting VCP selectively eliminates breast cancer cells while sparing non-transformed cells by inducing paraptosis, a non-apoptotic cell death mechanism characterized by endoplasmic reticulum and mitochondria dilation. Intriguingly, oncogenic HRas sensitizes non-transformed cells to VCP inhibition-mediated paraptosis. The susceptibility of cancer cells to VCP inhibition is attributed to the non-attenuation and recovery of protein synthesis under proteotoxic stress. Mechanistically, mTORC2/Akt activation and eIF3d-dependent translation contribute to translational rebound and amplification of proteotoxic stress. Furthermore, the ATF4/DDIT4 axis augments VCP inhibition-mediated paraptosis by activating Akt. Given that hyperactive Akt counteracts chemotherapeutic-induced apoptosis, VCP inhibition presents a promising therapeutic avenue to exploit Akt-associated vulnerabilities in cancer cells by triggering paraptosis while safeguarding normal cells. | - |
dc.identifier.bibliographicCitation | CELL DEATH & DISEASE, v.15, no.1, pp.48 | - |
dc.identifier.doi | 10.1038/s41419-024-06434-x | - |
dc.identifier.issn | 2041-4889 | - |
dc.identifier.scopusid | 2-s2.0-85182184486 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/74404 | - |
dc.identifier.wosid | 001142831700007 | - |
dc.language | 영어 | - |
dc.publisher | Springer Science and Business Media LLC | - |
dc.title | Akt enhances the vulnerability of cancer cells to VCP/p97 inhibition-mediated paraptosis | - |
dc.type | Article | - |
dc.description.isOpenAccess | TRUE | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.type.docType | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | TRANSLATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | BORTEZOMIB | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | ADENOVIRUS | - |
dc.subject.keywordPlus | OVERCOMES | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | EIF3D | - |
dc.subject.keywordPlus | MODEL | - |
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