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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/15905
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| Title: | DUSP22 inhibits lung tumorigenesis by suppression of EGFR/c-Met signaling |
| Authors: | Lin, HH;Chang, CW;Liao, YT;Yeh, SD;Lin, HP;Ho, HM;Cheung, CHY;Juan, HF;Chen, YR;Su, YW;Chen, LM;Tan, TH;Lin, WJ |
| Contributors: | Immunology Research Center;Institute of Molecular and Genomic Medicine |
| Abstract: | DUSP22, an atypical dual-specificity phosphatase enzyme, plays a significant role in regulating multiple kinase signaling pathways by dephosphorylation. Our study demonstrated that decreased DUSP22 expression is associated with shorter disease-free survival, advanced TNM (tumor, lymph nodes, and metastasis), cancer stage, and higher tumor grade in lung adenocarcinoma (LUAD) patients. Exogenous DUSP22 expression reduces the colony-forming capacity of lung cancer cells and inhibits xenograft tumor growth primarily by targeting EGFR and suppressing its activity through dephosphorylation. Knockdown of DUSP22 using shRNA enhances EGFR dependency in HCC827 lung cancer cells and increases sensitivity to gefitinib, an EGFR inhibitor. Consistently, genetic deletion of DUSP22 enhances EGFRdel (exon 19 deletion)-driven lung tumorigenesis and elevates EGFR activity. Pharmacological inhibition of DUSP22 activates EGFR, ERK1/2, and upregulates downstream PD-L1 expression. Additionally, lentiviral deletion of DUSP22 by shRNA enhances lung cancer cell migration through EGFR/c-Met and PD-L1-dependent pathways. Gefitinib, an EGFR inhibitor, mechanistically suppresses migration induced by DUSP22 deletion and inhibits c-Met activity. Furthermore, cabozantinib, a c-Met inhibitor, reduces migration and attenuates EGFR activation caused by DUSP22 deletion. Collectively, our findings support the hypothesis that loss of DUSP22 function in lung cancer cells confers a survival advantage by augmenting EGFR signaling, leading to increased activation of downstream c-Met, ERK1/2, and PD-L1 axis, ultimately contributing to the progression of advanced lung cancer. |
| Date: | 2024-06-14 |
| Relation: | Cell Death Discovery. 2024 Jun 14;10:Article number 285. |
| Link to: | http://dx.doi.org/10.1038/s41420-024-02038-8 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2058-7716&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:001248077300001 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85195949661 |
| Appears in Collections: | [林文傑] 期刊論文
[譚澤華] 期刊論文
[蘇郁文] 期刊論文
[陳怡榮] 期刊論文
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| ISI001248077300001.pdf | | 3660Kb | Adobe PDF | 66 | View/Open |
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