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Proteomics analysis of histone deacetylase inhibitor-resistant solid tumors reveals resistant signatures and potential drug combinations

文献类型：期刊论文

作者Hao, Bing-bing1; Ma, Ke2; Xu, Jun-yu1,3; Fan, Ru-feng1,4; Zhao, Wen-si5; Jia, Xing-long1,6; Zhai, Lin-hui1,3; Lee, Sangkyu7,8; Xie, Dong5; Tan, Min-jia1,2,3,4
刊名ACTA PHARMACOLOGICA SINICA
出版日期2024-02-21
页码11
ISSN号1671-4083
关键词solid tumor histone deacetylase inhibitor vorinostat (SAHA) drug resistance proteomics
DOI10.1038/s41401-024-01236-5
通讯作者Xu, Jun-yu(jyxu@simm.ac.cn) ; Xie, Dong(xiedong@tongji.edu.cn) ; Tan, Min-jia(mjtan@simm.ac.cn)
英文摘要Histone deacetylase inhibitors (HDACis) are important drugs for cancer therapy, but the indistinct resistant mechanisms of solid tumor therapy greatly limit their clinical application. In this study we conducted HDACi-perturbated proteomics and phosphoproteomics analyses in HDACi-sensitive and -resistant cell lines using a tandem mass tag (TMT)-based quantitative proteomic strategy. We found that the ribosome biogenesis proteins MRTO4, PES1, WDR74 and NOP16 vital to tumorigenesis might regulate the tumor sensitivity to HDACi. By integrating HDACi-perturbated protein signature with previously reported proteomics and drug sensitivity data, we predicted and validated a series of drug combination pairs potentially to enhance the sensitivity of HDACi in diverse solid tumor. Functional phosphoproteomic analysis further identified the kinase PDK1 and ROCK as potential HDACi-resistant signatures. Overall, this study reveals the potential HDACi-resistant signatures and may provide promising drug combination strategies to attenuate the resistance of solid tumor to HDACi.
WOS关键词RANDOMIZED PHASE-II ; T-CELL LYMPHOMA ; CANCER-THERAPY ; OPEN-LABEL ; ROMIDEPSIN ; PANOBINOSTAT ; SENSITIVITY ; VORINOSTAT ; ACTIVATION ; MECHANISMS
资助项目National Natural Science Foundation of China[32071432] ; National Natural Science Foundation of China[32171434] ; National Natural Science Foundation of China[82272943] ; National Natural Science Foundation of China[32322048] ; Youth Science and Technology Talents in Shanghai Sail Plan of China[21YF1456000] ; Young Elite Scientists Sponsorship Program by CAST[2022QNRC001] ; Shanghai Rising-Star Program[22QA1411100] ; Youth Innovation Promotion Association[CAS2021276] ; Sanofi Scholarship Program, Shanghai Committee of Science and Technology, China[21Y11913400] ; Guangdong High-level New R&D Institute, China[2019B090904008] ; Guangdong High-level Innovative Research Institute, China[2021B0909050003]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
出版者NATURE PUBL GROUP
WOS记录号WOS:001166441700001
源URL[http://119.78.100.183/handle/2S10ELR8/309581]  
专题中国科学院上海药物研究所
通讯作者Xu, Jun-yu; Xie, Dong; Tan, Min-jia
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Thorac Surg, Shanghai 200433, Peoples R China
6.Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 201203, Peoples R China
7.Kyungpook Natl Univ, Coll Pharm, Daegu, South Korea
8.Kyungpook Natl Univ, Res Inst Pharmaceut Sci, Daegu, South Korea
推荐引用方式
GB/T 7714		 Hao, Bing-bing,Ma, Ke,Xu, Jun-yu,et al. Proteomics analysis of histone deacetylase inhibitor-resistant solid tumors reveals resistant signatures and potential drug combinations[J]. ACTA PHARMACOLOGICA SINICA,2024:11.
APA Hao, Bing-bing.,Ma, Ke.,Xu, Jun-yu.,Fan, Ru-feng.,Zhao, Wen-si.,...&Tan, Min-jia.(2024).Proteomics analysis of histone deacetylase inhibitor-resistant solid tumors reveals resistant signatures and potential drug combinations.ACTA PHARMACOLOGICA SINICA,11.
MLA Hao, Bing-bing,et al."Proteomics analysis of histone deacetylase inhibitor-resistant solid tumors reveals resistant signatures and potential drug combinations".ACTA PHARMACOLOGICA SINICA (2024):11.

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来源：上海药物研究所

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