{"title":"IRAK2 过表达可通过调节 TRAF6 泛素化抑制前列腺癌的进展。","authors":"Yunfeng Shi, Chengshuai Wu, Chengyue Wang, Ying Shen, Anqi Jiang, Kai Cao, Xiaowu Liu, Xinying Jiang, Zhong Lv","doi":"10.1016/j.cellsig.2024.111508","DOIUrl":null,"url":null,"abstract":"<div><div>Prostate cancer is recognized as one of the most common tumors among men worldwide, yet the molecular mechanisms underlying its progression remain to be fully understood. In this study, we explored the role of interleukin-1 receptor-associated kinase 2 (IRAK2) in the progression of prostate cancer. We discovered that IRAK2 expression is downregulated in prostate cancer tissues and cells. Functional assays, including MTT, transwell assays, wound healing assays, and in vivo xenograft models, demonstrated that upregulation of IRAK2 significantly inhibited prostate cancer cell viability, migration, invasion, and tumor growth. Furthermore, we found that IRAK2 modulates the biological functions of prostate cancer by interacting with TNF receptor-associated factor 6 (TRAF6). Knockdown of TRAF6 reversed the suppressive effects of IRAK2 overexpression on prostate cancer cell progression. Additionally, IRAK2 was found to suppress the ubiquitination and degradation of TRAF6 in prostate cancer cells. IRAK2 also influenced the sensitivity of prostate cancer cells to docetaxel (DTX), and silencing IRAK2 reversed the anti-tumor effects of DTX on prostate cancer cells. Our findings suggest that IRAK2 functions as a tumor suppressor in prostate cancer and may serve as a potential therapeutic target for developing effective treatments for prostate cancer.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"125 ","pages":"Article 111508"},"PeriodicalIF":4.4000,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"IRAK2 overexpression restrains prostate cancer progression by regulation of TRAF6 ubiquitination\",\"authors\":\"Yunfeng Shi, Chengshuai Wu, Chengyue Wang, Ying Shen, Anqi Jiang, Kai Cao, Xiaowu Liu, Xinying Jiang, Zhong Lv\",\"doi\":\"10.1016/j.cellsig.2024.111508\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Prostate cancer is recognized as one of the most common tumors among men worldwide, yet the molecular mechanisms underlying its progression remain to be fully understood. In this study, we explored the role of interleukin-1 receptor-associated kinase 2 (IRAK2) in the progression of prostate cancer. We discovered that IRAK2 expression is downregulated in prostate cancer tissues and cells. Functional assays, including MTT, transwell assays, wound healing assays, and in vivo xenograft models, demonstrated that upregulation of IRAK2 significantly inhibited prostate cancer cell viability, migration, invasion, and tumor growth. Furthermore, we found that IRAK2 modulates the biological functions of prostate cancer by interacting with TNF receptor-associated factor 6 (TRAF6). Knockdown of TRAF6 reversed the suppressive effects of IRAK2 overexpression on prostate cancer cell progression. Additionally, IRAK2 was found to suppress the ubiquitination and degradation of TRAF6 in prostate cancer cells. IRAK2 also influenced the sensitivity of prostate cancer cells to docetaxel (DTX), and silencing IRAK2 reversed the anti-tumor effects of DTX on prostate cancer cells. Our findings suggest that IRAK2 functions as a tumor suppressor in prostate cancer and may serve as a potential therapeutic target for developing effective treatments for prostate cancer.</div></div>\",\"PeriodicalId\":9902,\"journal\":{\"name\":\"Cellular signalling\",\"volume\":\"125 \",\"pages\":\"Article 111508\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2024-11-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cellular signalling\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0898656824004832\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular signalling","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0898656824004832","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
IRAK2 overexpression restrains prostate cancer progression by regulation of TRAF6 ubiquitination
Prostate cancer is recognized as one of the most common tumors among men worldwide, yet the molecular mechanisms underlying its progression remain to be fully understood. In this study, we explored the role of interleukin-1 receptor-associated kinase 2 (IRAK2) in the progression of prostate cancer. We discovered that IRAK2 expression is downregulated in prostate cancer tissues and cells. Functional assays, including MTT, transwell assays, wound healing assays, and in vivo xenograft models, demonstrated that upregulation of IRAK2 significantly inhibited prostate cancer cell viability, migration, invasion, and tumor growth. Furthermore, we found that IRAK2 modulates the biological functions of prostate cancer by interacting with TNF receptor-associated factor 6 (TRAF6). Knockdown of TRAF6 reversed the suppressive effects of IRAK2 overexpression on prostate cancer cell progression. Additionally, IRAK2 was found to suppress the ubiquitination and degradation of TRAF6 in prostate cancer cells. IRAK2 also influenced the sensitivity of prostate cancer cells to docetaxel (DTX), and silencing IRAK2 reversed the anti-tumor effects of DTX on prostate cancer cells. Our findings suggest that IRAK2 functions as a tumor suppressor in prostate cancer and may serve as a potential therapeutic target for developing effective treatments for prostate cancer.
期刊介绍:
Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo.
Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.