LC3B upregulation by NANOG promotes immune resistance and stem-like property through hyperactivation of EGFR signaling in immune-refractory tumor cells
DC Field | Value | Language |
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dc.contributor.author | Kim, Suyeon | - |
dc.contributor.author | Cho, Hanbyoul | - |
dc.contributor.author | Hong, Soon-Oh | - |
dc.contributor.author | Oh, Se Jin | - |
dc.contributor.author | Lee, Hyo-Jung | - |
dc.contributor.author | Cho, Eunho | - |
dc.contributor.author | Woo, Seon Rang | - |
dc.contributor.author | Song, Joon Seon | - |
dc.contributor.author | Chung, Joon-Yong | - |
dc.contributor.author | Son, Sung Wook | - |
dc.contributor.author | Yoon, Sang Min | - |
dc.contributor.author | Jeon, Yu-Min | - |
dc.contributor.author | Jeon, Seunghyun | - |
dc.contributor.author | Yee, Cassian | - |
dc.contributor.author | Lee, Kyung-Mi | - |
dc.contributor.author | Hewitt, Stephen M. | - |
dc.contributor.author | Kim, Jae-Noon | - |
dc.contributor.author | Song, Kwon-Ho | - |
dc.contributor.author | Kim, Tae Woo | - |
dc.date.accessioned | 2021-12-08T02:42:02Z | - |
dc.date.available | 2021-12-08T02:42:02Z | - |
dc.date.created | 2021-08-30 | - |
dc.date.issued | 2021 | - |
dc.identifier.issn | 1554-8627 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/130228 | - |
dc.description.abstract | Immune selection drives tumor cells to acquire refractory phenotypes. We previously demonstrated that cytotoxic T lymphocyte (CTL)-mediated immune pressure enriches NANOG(+)tumor cells with stem-like and immune-refractory properties that make them resistant to CTLs. Here, we report that the emergence of refractory phenotypes is highly associated with an aberrant macroautophagic/autophagic state of the NANOG(+)tumor cells and that the autophagic phenotype arises through transcriptional induction ofMAP1LC3B/LC3Bby NANOG. Furthermore, we found that upregulation of LC3B expression contributes to an increase in EGF secretion. The subsequent hyperactivation of EGFR-AKT signaling rendered NANOG(+)tumor cells resistant to CTL killing. The NANOG-LC3B-p-EGFR axis was preserved across various types of human cancer and correlated negatively with the overall survival of cervical cancer patients. Inhibition of LC3B in immune-refractory tumor models rendered tumors susceptible to adoptive T-cell transfer, as well as PDCD1/PD-1 blockade, and led to successful, long-term control of the disease. Thus, our findings demonstrate a novel link among immune-resistance, stem-like phenotypes, and LC3B-mediated autophagic secretion in immune-refractory tumor cells, and implicate the LC3B-p-EGFR axis as a central molecular target for controlling NANOG(+)immune-refractory cancer. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | TAYLOR & FRANCIS INC | - |
dc.subject | CANCER | - |
dc.subject | AUTOPHAGY | - |
dc.subject | ESCAPE | - |
dc.subject | EXPRESSION | - |
dc.title | LC3B upregulation by NANOG promotes immune resistance and stem-like property through hyperactivation of EGFR signaling in immune-refractory tumor cells | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Tae Woo | - |
dc.identifier.doi | 10.1080/15548627.2020.1805214 | - |
dc.identifier.scopusid | 2-s2.0-85089460863 | - |
dc.identifier.wosid | 000559547500001 | - |
dc.identifier.bibliographicCitation | AUTOPHAGY, v.17, no.8, pp.1978 - 1997 | - |
dc.relation.isPartOf | AUTOPHAGY | - |
dc.citation.title | AUTOPHAGY | - |
dc.citation.volume | 17 | - |
dc.citation.number | 8 | - |
dc.citation.startPage | 1978 | - |
dc.citation.endPage | 1997 | - |
dc.type.rims | ART | - |
dc.type.docType | Article; Early Access | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | AUTOPHAGY | - |
dc.subject.keywordPlus | ESCAPE | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordAuthor | Cancer immunoediting | - |
dc.subject.keywordAuthor | EGFR | - |
dc.subject.keywordAuthor | immune resistance | - |
dc.subject.keywordAuthor | immunotherapy | - |
dc.subject.keywordAuthor | LC3B | - |
dc.subject.keywordAuthor | MAP1LC3B | - |
dc.subject.keywordAuthor | NANOG | - |
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