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창의적인 신지식 창출과 산업계와의 협력적 네트워크 구축

금주의 우수논문

SCI-E Article
PLK1-mediated phosphorylation of 13-catenin enhances its stability and transcriptional activity for extracellular matrix remodeling in metastatic NSCLC
임형신
  1. 성명
    임형신
  2. 소속
    약학대학 약학과
  3. 캠퍼스
  4. 우수선정주
    2023년 03월 4째주
Author
Kim, Da-Eun (Dept Pharm); Shin, Sol-Bi (Dept Pharm); Kim, Chang-Hyeon (Dept Pharm); Kim, Yeo-Bin (Dept Pharm); Oh, Hyun-Ji (Dept Pharm); Yim, Hyungshin (Dept Pharm); Yim, Hyungshin (Inst Pharmaceut Sci & Technol); 임형신 (Dept Pharm) corresponding author;
Corresponding Author Info
Yim, H (corresponding author), Hanyang Univ, Inst Pharmaceut Sci & Technol, Coll Pharm, Dept Pharm, Ansan 15588, Gyeonggi, South Korea.
E-mail
이메일hsyim@hanyang.ac.kr
Document Type
Article
Source
THERANOSTICS Volume:13 Issue:3 Pages:1198-1216 Published:2023
Times Cited
0
External Information
http://dx.doi.org/10.7150/thno.79318
Abstract
Rationale: 13-catenin is a component for cell adhesion and a transcriptional coactivator in epithelial-mesenchymal transition (EMT). Previously we found that catalytically active PLK1 drives EMT in non-small cell lung cancer (NSCLC), upregulating extracellular matrix factors including TSG6, laminin y2, and CD44. To understand the underlying mechanism and clinical significance of PLK1 and 13-catenin in NSCLC, their relationship and function in metastatic regulation were investigated.Methods: The clinical relevance between the survival rate of NSCLC patients and the expression of PLK1 and 13-catenin was analyzed by a KM plot. Immunoprecipitation, kinase assay, LC-MS/MS spectrometry, and site-directed mutagenesis were performed to reveal their interaction and phosphorylation. A lentiviral doxycycline-inducible system, Transwell-based 3D culture, tail-vein injection model, confocal microscopy, and chromatin immunoprecipitation assays were used to elucidate the function of phosphorylated 13-catenin in the EMT of NSCLC.Results: Clinical analysis revealed that the high expression of CTNNB1/PLK1 was inversely correlated with the survival rates of 1,292 NSCLC patients, especially in metastatic NSCLC. In TGF-13-induced or active PLK1-driven EMT, 13-catenin, PLK1, TSG6, laminin y2, and CD44 were concurrently upregulated. 13-catenin is a binding partner of PLK1 in TGF-13-induced EMT and is phosphorylated at S311. Phosphomimetic 13-catenin promotes cell motility, invasiveness of NSCLC cells, and metastasis in a tail-vein injection mouse model. Its upregulated stability by phosphorylation enhances transcriptional activity through nuclear translocation for the expression of laminin y2, CD44, and c-Jun, therefore enhancing PLK1 expression by AP-1.Conclusions: Our findings provide evidence for the critical role of the PLK1/beta-catenin/AP-1 axis in metastatic NSCLC, implying that 13-catenin and PLK1 may serve as a molecular target and prognostic indicator of the therapeutic response in metastatic NSCLC patients.
Web of Science Categories
Medicine, Research & Experimental
Funding
Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [NRF-2017R1A2B2012301, NRF-2020R1A2C2008672]
Language
English
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