The COP9 signalosome stabilized MALT1 promotes Non-Small Cell Lung Cancer progression through activation of NF-κB pathway.

Autor: Wang Y; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China.; Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong Province, China., Deng X; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China., Xie J; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China., Lu T; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China., Qian R; Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China., Guo Z; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China., Zeng X; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China., Liao J; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China., Ding Z; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China. dingzh@smu.edu.cn., Zhou M; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China. lkzmj@smu.edu.cn., Niu X; Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, China. niuxl@smu.edu.cn.; Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong Province, China. niuxl@smu.edu.cn.
Jazyk: angličtina
Zdroj: Cell biology and toxicology [Cell Biol Toxicol] 2024 Jun 12; Vol. 40 (1), pp. 45. Date of Electronic Publication: 2024 Jun 12.
DOI: 10.1007/s10565-024-09888-z
Abstrakt: MALT1 has been implicated as an upstream regulator of NF-κB signaling in immune cells and tumors. This study determined the regulatory mechanisms and biological functions of MALT1 in non-small cell lung cancer (NSCLC). In cell culture and orthotopic xenograft models, MALT1 suppression via gene expression interference or protein activity inhibition significantly impaired malignant phenotypes and enhanced radiation sensitivity of NSCLC cells. CSN5, the core subunit of COP9 signalosome, was firstly verified to stabilize MALT1 via disturbing the interaction with E3 ligase FBXO3. Loss of FBXO3 in NSCLC cells reduced MALT1 ubiquitination and promoted its accumulation, which was reversed by CSN5 interference. An association between CSN5/FBXO3/MALT1 regulatory axis and poor prognosis in NSCLC patients was identified. Our findings revealed the detail mechanism of continuous MALT1 activation in NF-κB signaling, highlighting its significance as predictor and potential therapeutic target in NSCLC.
(© 2024. The Author(s).)
Databáze: MEDLINE
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