Inhibition of PI3 kinase isoform p110a suppresses neuroblastoma growth and induces the reduction of Anaplastic Lymphoma Kinase

作者全名："Guo, Yue; Guo, Donghao; Zhang, Shaoting; Zhang, Yuan; He, Xiaoyan; Jiang, Xiaohua; Chan, Andrew Man-Lok; Zou, Lin; Sun, Jianmin; Zhao, Hui"

作者地址："[Guo, Yue; Guo, Donghao; Zhang, Yuan; Jiang, Xiaohua; Chan, Andrew Man-Lok; Zhao, Hui] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Key Lab Regenerat Med, Hong Kong, Peoples R China; [Zhang, Shaoting; Sun, Jianmin] Ningxia Med Univ, Sci & Technol Ctr, Sch Basic Med Sci, NHC Key Lab Metab Cardiovasc Dis Res, 1160 Shengli St, Yinchuan 750004, Peoples R China; [He, Xiaoyan] Chongqing Med Univ, Newborn Screening Ctr & Ctr Clin Mol Med Childrens, Chongqing 400014, Peoples R China; [Zou, Lin] Shanghai Jiao Tong Univ Sch Med, Shanghai Childrens Hosp, Inst Pediat Infect, Clin Res Unit, Shanghai 200062, Peoples R China; [Zhao, Hui] Chinese Univ Hong Kong Joint, Kunming Inst Zool Chinese Acad Sci, Lab Bioresources & Mol Res Common Dis, Hong Kong, Peoples R China; [Zhao, Hui] Chinese Univ Hong Kong, Hong Kong Branch CAS Ctr Excellence Anim Evolut &, Hong Kong, Peoples R China"

通信作者："Zhao, H (通讯作者)，Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Key Lab Regenerat Med, Hong Kong, Peoples R China.; Sun, JM (通讯作者)，Ningxia Med Univ, Sci & Technol Ctr, Sch Basic Med Sci, NHC Key Lab Metab Cardiovasc Dis Res, 1160 Shengli St, Yinchuan 750004, Peoples R China.; Zhao, H (通讯作者)，Chinese Univ Hong Kong Joint, Kunming Inst Zool Chinese Acad Sci, Lab Bioresources & Mol Res Common Dis, Hong Kong, Peoples R China.; Zhao, H (通讯作者)，Chinese Univ Hong Kong, Hong Kong Branch CAS Ctr Excellence Anim Evolut &, Hong Kong, Peoples R China."

来源：CELL AND BIOSCIENCE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000906116100002

JCR分区：Q1

影响因子：7.5

年份：2022

卷号：12

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Neuroblastoma; PI3 Kinase; p110 alpha; PIK3CA; ALK; Alpelisib

摘要："Background: In neuroblastoma, hyperactivation of the PI3K signaling pathway has been correlated with aggressive neuroblastomas, suggesting PI3Ks as promising targets for the treatment of neuroblastoma. However, the oncogenic roles of individual PI3K isoforms in neuroblastoma remain elusive. Results: We found that PI3K isoform p110 alpha was expressed at higher levels in neuroblastoma tissues compared with normal tissues, and its high expression was correlated with an unfavorable prognosis of neuroblastoma. Accordingly, PI3K activation in neuroblastoma cells was predominantly mediated by p110 alpha but not by p110 beta or p110 delta. Suppression of p110 alpha inhibited the growth of neuroblastoma cells both in vitro and in vivo, suggesting a crucial role of p110 alpha in the tumorigenesis of neuroblastoma. Mechanistically, inhibition of p110 alpha decreased anaplastic lymphoma kinase (ALK) in neuroblastoma cells by decreasing its protein stability. Conclusions: In this study, we investigated the oncogenic roles of PI3K isoforms in neuroblastoma. Our data shed light on PI3K isoform p110 alpha in the tumorigenesis of neuroblastoma, and strongly suggest the p110 alpha inhibitors as potential drugs in treating neuroblastoma."

基金机构："National Key R&D Program of China, Synthetic Biology Research; Research Grants Council of Hong Kong [2019YFA0900450]; National Natural Science Foundation of China [14167017, 14112618, 14119120]; Hong Kong Branch of the CAS Center for Excellence in Animal Evolution and Genetics [82160521]; Chinese University of Hong Kong; [8601012]"

基金资助正文："This work was supported by the National Key R & D Program of China, Synthetic Biology Research (No. 2019YFA0900450).The Research Grants Council of Hong Kong (14167017, 14112618, and 14119120) to HZ. National Natural Science Foundation of China (82160521) to JS. Additional support was provided by the Hong Kong Branch of the CAS Center for Excellence in Animal Evolution and Genetics, The Chinese University of Hong Kong (8601012)."