RNF25 promotes gefitinib resistance in EGFR-mutant NSCLC cells by inducing NF-κB-mediated ERK reactivation

Cited 16 time in scopus
Metadata Downloads

Full metadata record

DC FieldValueLanguage
dc.contributor.authorJung Hee Cho-
dc.contributor.authorYeon Mi You-
dc.contributor.authorYoung Il Yeom-
dc.contributor.authorDong Chul Lee-
dc.contributor.authorBo Kyung Kim-
dc.contributor.authorMi Sun Won-
dc.contributor.authorB C Cho-
dc.contributor.authorMingho Kang-
dc.contributor.authorSeulki Park-
dc.contributor.authorSuk-Jin Yang-
dc.contributor.authorJang Seong Kim-
dc.contributor.authorJung Ae Kim-
dc.contributor.authorKyung Chan Park-
dc.date.accessioned2018-07-19T16:30:28Z-
dc.date.available2018-07-19T16:30:28Z-
dc.date.issued2018-
dc.identifier.issn20414889-
dc.identifier.uri10.1038/s41419-018-0651-5ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/17891-
dc.description.abstractNon-small cell lung cancer (NSCLC) patients with EGFR mutations initially respond well to EGFR tyrosine kinase inhibitors (TKIs) but eventually exhibit acquired or innate resistance to the therapies typically due to gene mutations, such as EGFR T790M mutation or a second mutation in the downstream pathways of EGFR. Importantly, a significant portion of NSCLC patients shows TKI resistance without any known mechanisms, calling more comprehensive studies to reveal the underlying mechanisms. Here, we investigated a synthetic lethality with gefitinib using a genome-wide RNAi screen in TKI-resistant EGFR-mutant NSCLC cells, and identified RNF25 as a novel factor related to gefitinib resistance. Depletion of RNF25 expression substantially sensitized NSCLC cells to gefitinib treatment, while forced expression of RNF25 augmented gefitinib resistance in sensitive cells. We demonstrated that RNF25 mediates NF-κB activation in gefitinib-treated cells, which, in turn, induces reactivation of ERK signal to cause the drug resistance. We identified that the ERK reactivation occurs via the function of cytokines, such as IL-6, whose expression is transcriptionally induced in a gefitinib-dependent manner by RNF25-mediated NF-κB signals. These results suggest that RNF25 plays an essential role in gefitinib resistance of NSCLC by mediating cross-talk between NF-κB and ERK pathways, and provide a novel target for the combination therapy to overcome TKI resistance of NSCLC-
dc.publisherSpringer-Nature Pub Group-
dc.titleRNF25 promotes gefitinib resistance in EGFR-mutant NSCLC cells by inducing NF-κB-mediated ERK reactivation-
dc.title.alternativeRNF25 promotes gefitinib resistance in EGFR-mutant NSCLC cells by inducing NF-κB-mediated ERK reactivation-
dc.typeArticle-
dc.citation.titleCell Death & Disease-
dc.citation.number6-
dc.citation.endPage587-
dc.citation.startPage587-
dc.citation.volume9-
dc.contributor.affiliatedAuthorYoung Il Yeom-
dc.contributor.affiliatedAuthorDong Chul Lee-
dc.contributor.affiliatedAuthorBo Kyung Kim-
dc.contributor.affiliatedAuthorMi Sun Won-
dc.contributor.affiliatedAuthorMingho Kang-
dc.contributor.affiliatedAuthorJung Ae Kim-
dc.contributor.affiliatedAuthorKyung Chan Park-
dc.contributor.alternativeName조정희-
dc.contributor.alternativeName유연미-
dc.contributor.alternativeName염영일-
dc.contributor.alternativeName이동철-
dc.contributor.alternativeName김보경-
dc.contributor.alternativeName원미선-
dc.contributor.alternativeName조병철-
dc.contributor.alternativeName강민호-
dc.contributor.alternativeName박슬기-
dc.contributor.alternativeName양석진-
dc.contributor.alternativeName김장성-
dc.contributor.alternativeName김정애-
dc.contributor.alternativeName박경찬-
dc.identifier.bibliographicCitationCell Death & Disease, vol. 9, no. 6, pp. 587-587-
dc.identifier.doi10.1038/s41419-018-0651-5-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.