DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Byung Soo | ko |
dc.contributor.author | Park, Dong Il | ko |
dc.contributor.author | Lee, Da-Hye | ko |
dc.contributor.author | Lee, Jeong Eun | ko |
dc.contributor.author | Yeo, Min-kyung | ko |
dc.contributor.author | Park, Yeon Hee | ko |
dc.contributor.author | Lim, Dae Sik | ko |
dc.contributor.author | Choi, Wonyoung | ko |
dc.contributor.author | Lee, Da-Hye | ko |
dc.contributor.author | Yoo, Geon | ko |
dc.contributor.author | Kim, Hanbyul | ko |
dc.contributor.author | Kang, Dahyun | ko |
dc.contributor.author | Moon, Jae Young | ko |
dc.contributor.author | Jung, Sung Soo | ko |
dc.contributor.author | Kim, Ju Ock | ko |
dc.contributor.author | Cho, Sang Yeon | ko |
dc.contributor.author | Park, Hee Sun | ko |
dc.contributor.author | Chung, Chaeuk | ko |
dc.date.accessioned | 2017-09-25T05:11:39Z | - |
dc.date.available | 2017-09-25T05:11:39Z | - |
dc.date.created | 2017-09-11 | - |
dc.date.created | 2017-09-11 | - |
dc.date.issued | 2017-09 | - |
dc.identifier.citation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.491, no.2, pp.493 - 499 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.uri | http://hdl.handle.net/10203/225986 | - |
dc.description.abstract | Developments of EGFR-TKI and immunotherapy targeting the PD1/13D-L1 pathway are considered most important medical breakthroughs in lung cancer treatment. Nowadays, 3rd generation EGFR TKI is widely used for T790M positive 1st and 2nd EGFR-TKI resistant lung cancer patients. Immunotherapy is powerful option for lung cancer patients without drug targets and chemotherapy resistant patients. It also has changed the concept of conventional anti-cancer therapy in the point of regulating tumor microenvironment. There are many studies linking these two important pathways. Recent studies demonstrated that PD-L1 expression is significantly correlated to the mutation status of EGFR, and activation of EGFR signaling can also induce the expression of PD-L1. However, the real linker between PD-Li and EGFR signaling remains to be revealed. Our previous study revealed that the Hippo pathway effector YAP confers EGFR-TKI resistance in lung adenocarcinoma, and inhibition of YAP restores sensitivity to EGFR-TKIs. Thus, we examined whether PD-L1 is relevant, in terms of conferring EGFR-TKI resistance and whether YAP directly regulates the expression of PD-L1 in this context. First, we compared the expression levels of PD-L1 and YAP between EGFR-TKI-resistant PC9 cells and the parental PC9 adenocarcinoma cells. The expression levels of both YAP and PD-L1 were markedly higher in the EGFR-TKI-resistant cells compared to the parental cells, suggesting differential expression pattern between two cell types. YAP knockdown significantly decreased the expression of PD-L1 in the EGFR-TKI-resistant cells, while YAP overexpression increased the expression of PD-Li in the parental PC9 cells. Then, our results revealed that YAP regulates the transcription of PD-L1, and the YAP/TEAD complex binds to the PD-L1 promoter. Surprisingly, knockdown of PDv was sufficient to decrease cell proliferation and wound healing in the EGFR-TKI-resistant PC9 cells. These data suggest a PD1-independent oncogenic function of PD-L1. The Hippo effector YAP plays a crucial role in linking the PD-L1 and EGFR-TKI resistance by directly regulating the expression of PD-L1 in lung cancer. Targeting PD-L1 directly or via YAP could provide an effective therapeutic strategy for EGFR-TKI-resistant lung adenocarcinoma. (C) 2017 Elsevier Inc. All rights reserved. | - |
dc.language | English | - |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | - |
dc.subject | SIGNALING PATHWAY | - |
dc.subject | CANCER | - |
dc.subject | SURVIVAL | - |
dc.subject | TARGET | - |
dc.subject | ROLES | - |
dc.subject | NSCLC | - |
dc.subject | CELLS | - |
dc.title | Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcilloma | - |
dc.type | Article | - |
dc.identifier.wosid | 000408291100038 | - |
dc.identifier.scopusid | 2-s2.0-85025173956 | - |
dc.type.rims | ART | - |
dc.citation.volume | 491 | - |
dc.citation.issue | 2 | - |
dc.citation.beginningpage | 493 | - |
dc.citation.endingpage | 499 | - |
dc.citation.publicationname | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.identifier.doi | 10.1016/j.bbrc.2017.07.007 | - |
dc.contributor.localauthor | Lim, Dae Sik | - |
dc.contributor.nonIdAuthor | Lee, Byung Soo | - |
dc.contributor.nonIdAuthor | Park, Dong Il | - |
dc.contributor.nonIdAuthor | Lee, Da-Hye | - |
dc.contributor.nonIdAuthor | Lee, Jeong Eun | - |
dc.contributor.nonIdAuthor | Yeo, Min-kyung | - |
dc.contributor.nonIdAuthor | Park, Yeon Hee | - |
dc.contributor.nonIdAuthor | Yoo, Geon | - |
dc.contributor.nonIdAuthor | Kang, Dahyun | - |
dc.contributor.nonIdAuthor | Moon, Jae Young | - |
dc.contributor.nonIdAuthor | Jung, Sung Soo | - |
dc.contributor.nonIdAuthor | Kim, Ju Ock | - |
dc.contributor.nonIdAuthor | Cho, Sang Yeon | - |
dc.contributor.nonIdAuthor | Park, Hee Sun | - |
dc.contributor.nonIdAuthor | Chung, Chaeuk | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | PD-Li | - |
dc.subject.keywordAuthor | YAP1 | - |
dc.subject.keywordAuthor | EGFR | - |
dc.subject.keywordAuthor | Adenocarcinoma | - |
dc.subject.keywordAuthor | Immunotherapy | - |
dc.subject.keywordPlus | SIGNALING PATHWAY | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | SURVIVAL | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | ROLES | - |
dc.subject.keywordPlus | NSCLC | - |
dc.subject.keywordPlus | CELLS | - |
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