Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Nayoung | - |
dc.contributor.author | Cho, Ahye | - |
dc.contributor.author | Watanabe, Hideo | - |
dc.contributor.author | Choi, Yoon-La | - |
dc.contributor.author | Aziz, Meraj | - |
dc.contributor.author | Kassner, Michelle | - |
dc.contributor.author | Joung, Je-Gun | - |
dc.contributor.author | Park, Angela K. J. | - |
dc.contributor.author | Francis, Joshua M. | - |
dc.contributor.author | Bae, Joon Seol | - |
dc.contributor.author | Ahn, Soo-min | - |
dc.contributor.author | Kim, Kyoung-Mee | - |
dc.contributor.author | Park, Joon Oh | - |
dc.contributor.author | Park, Woong-Yang | - |
dc.contributor.author | Ahn, Myung-Ju | - |
dc.contributor.author | Park, Keunchil | - |
dc.contributor.author | Koo, Jaehyung | - |
dc.contributor.author | Yin, Hongwei Holly | - |
dc.contributor.author | Cho, Jeonghee | - |
dc.date.available | 2017-07-11T05:33:51Z | - |
dc.date.created | 2017-04-10 | - |
dc.date.issued | 2016-03 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/2707 | - |
dc.description.abstract | Therapies targeting the tyrosine kinase activity of Epidermal Growth Factor Receptor (EGFR) have been proven to be effective in treating a subset of non-small cell lung cancer (NSCLC) patients harboring activating EGFR mutations. Inevitably these patients develop resistance to the EGFR-targeted tyrosine kinase inhibitors (TKIs). Here, we performed integrated genomic analyses using an in vitro system to uncover alternative genomic mechanisms responsible for acquired resistance to EGFR-TKIs. Specifically, we identified 80 genes whose expression is significantly increased in the erlotinib-resistant clones. RNAi-based systematic synthetic lethal screening of these candidate genes revealed that suppression of one upregulated transcript, SCRN1, a secernin family member, restores sensitivity to erlotinib by enhancing inhibition of PI3K/AKT signaling pathway. Furthermore, immunohistochemical analysis revealed increased levels of SCRN1 in 5 of 11 lung tumor specimens from EGFR-TKIs resistant patients. Taken together, we propose that upregulation of SCRN1 is an additional mechanism associated with acquired resistance to EGFR-TKIs and that its suppression serves as a novel therapeutic strategy to overcome drug resistance in these patients. | - |
dc.language | English | - |
dc.publisher | Impact Journals LLC | - |
dc.title | Integrated genomic approaches identify upregulation of SCRN1 as a novel mechanism associated with acquired resistance to erlotinib in PC9 cells harboring oncogenic EGFR mutation | - |
dc.type | Article | - |
dc.identifier.doi | 10.18632/oncotarget.7318 | - |
dc.identifier.scopusid | 2-s2.0-84971668242 | - |
dc.identifier.bibliographicCitation | Oncotarget, v.7, no.12, pp.13797 - 13809 | - |
dc.subject.keywordAuthor | EGFR | - |
dc.subject.keywordAuthor | SCRN1 | - |
dc.subject.keywordAuthor | lung adenocarcinoma | - |
dc.subject.keywordAuthor | erlotinib resistance | - |
dc.subject.keywordPlus | Animal Experiment | - |
dc.subject.keywordPlus | Animal Model | - |
dc.subject.keywordPlus | Article | - |
dc.subject.keywordPlus | Cancer Resistance | - |
dc.subject.keywordPlus | Controlled Study | - |
dc.subject.keywordPlus | EGFR | - |
dc.subject.keywordPlus | Epidermal Growth Factor Receptor | - |
dc.subject.keywordPlus | Epidermal Growth Factor Receptor Gene | - |
dc.subject.keywordPlus | Erlotinib | - |
dc.subject.keywordPlus | Erlotinib Resistance | - |
dc.subject.keywordPlus | Gene | - |
dc.subject.keywordPlus | Gene Expression | - |
dc.subject.keywordPlus | Gene Mutation | - |
dc.subject.keywordPlus | Genetic Association | - |
dc.subject.keywordPlus | Genome Analysis | - |
dc.subject.keywordPlus | Human | - |
dc.subject.keywordPlus | Human Tissue | - |
dc.subject.keywordPlus | Immunohistochemistry | - |
dc.subject.keywordPlus | In Vitro Study | - |
dc.subject.keywordPlus | In Vivo Study | - |
dc.subject.keywordPlus | Lung Adenocarcinoma | - |
dc.subject.keywordPlus | Male | - |
dc.subject.keywordPlus | Mouse | - |
dc.subject.keywordPlus | Nonhuman | - |
dc.subject.keywordPlus | Phosphatidylinositol 3 Kinase | - |
dc.subject.keywordPlus | Protein Kinase B | - |
dc.subject.keywordPlus | RNA Sequence | - |
dc.subject.keywordPlus | SCRN1 | - |
dc.subject.keywordPlus | SCRN1 Gene | - |
dc.subject.keywordPlus | Signal Transduction | - |
dc.subject.keywordPlus | Up-Regulation | - |
dc.citation.endPage | 13809 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 13797 | - |
dc.citation.title | Oncotarget | - |
dc.citation.volume | 7 | - |
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