Impaired AKT signaling and lung tumorigenesis by PIERCE1 ablation in KRAS-mutant non-small cell lung cancer
DC Field | Value | Language |
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dc.contributor.author | Roh, Jae-il | - |
dc.contributor.author | Lee, Jaehoon | - |
dc.contributor.author | Sung, Young-Hoon | - |
dc.contributor.author | Oh, Jahyun | - |
dc.contributor.author | Hyeon, Do Young | - |
dc.contributor.author | Kim, Yujin | - |
dc.contributor.author | Lee, Seungeon | - |
dc.contributor.author | Devkota, Sushil | - |
dc.contributor.author | Kim, Hye Jeong | - |
dc.contributor.author | Park, Bomin | - |
dc.contributor.author | Nam, Taewook | - |
dc.contributor.author | Song, Yaechan | - |
dc.contributor.author | Kim, Yonghwan | - |
dc.contributor.author | Hwang, Daehee | - |
dc.contributor.author | Lee, Han-Woong | - |
dc.date.available | 2021-02-22T05:23:07Z | - |
dc.date.issued | 2020-09 | - |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.issn | 1476-5594 | - |
dc.identifier.uri | https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/1251 | - |
dc.description.abstract | KRAS-mutant non-small cell lung cancer (NSCLC) is a major lung cancer subtype that leads to many cancer-related deaths worldwide. Although numerous studies on KRAS-mutant type NSCLC have been conducted, new oncogenic or tumor suppressive genes need to be detected because a large proportion of NSCLC patients does not respond to currently used therapeutics. Here, we show the tumor-promoting function of a cell cycle-related protein, PIERCE1, in KRAS-mutant NSCLC. Mechanistically, PIERCE1 depletion inhibits cell growth and AKT phosphorylation (pAKT) at S473, which is particularly observed in KRAS-mutant lung cancers. Analyses of AKT-related genes using microarray, immunoblotting, and real-time quantitative PCR indicated that PIERCE1 negatively regulates the gene expression of the AKT suppressor, TRIB3, through the CHOP pathway, which is a key regulatory pathway for TRIB3 expression. Similarly, in vivo analyses of PIERCE1 depletion in the KRAS mutation-related lung cancer mouse models revealed the suppressive effect of PIERCE1 knockout in urethane- and KRAS(G12D)-induced lung tumorigenesis with decreased pAKT levels observed in the tumors. Tissue microarrays of human lung cancers indicated the expression of PIERCE1 in 83% of lung cancers and its correlation with pAKT expression. Thus, we illustrate how PIERCE1 depletion may serve as a therapeutic strategy against KRAS-mutant NSCLC and propose the clinical benefit of PIERCE1. | - |
dc.format.extent | 12 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.title | Impaired AKT signaling and lung tumorigenesis by PIERCE1 ablation in KRAS-mutant non-small cell lung cancer | - |
dc.type | Article | - |
dc.publisher.location | 영국 | - |
dc.identifier.doi | 10.1038/s41388-020-01399-5 | - |
dc.identifier.scopusid | 2-s2.0-85088792964 | - |
dc.identifier.wosid | 000553757600001 | - |
dc.identifier.bibliographicCitation | ONCOGENE, v.39, no.36, pp 5876 - 5887 | - |
dc.citation.title | ONCOGENE | - |
dc.citation.volume | 39 | - |
dc.citation.number | 36 | - |
dc.citation.startPage | 5876 | - |
dc.citation.endPage | 5887 | - |
dc.type.docType | Article; Early Access | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.subject.keywordPlus | ER STRESS | - |
dc.subject.keywordPlus | PI3K/AKT/MTOR PATHWAY | - |
dc.subject.keywordPlus | INDUCIBLE GENE | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | SURVIVAL | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | METABOLISM | - |
dc.subject.keywordPlus | INHIBITORS | - |
dc.identifier.url | https://www.nature.com/articles/s41388-020-01399-5 | - |
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