Inhibition of PI3 kinase isoform p110α suppresses neuroblastoma growth and induces the reduction of Anaplastic Lymphoma Kinase

Yue Guo; Donghao Guo; Shaoting Zhang; Yuan Zhang; Xiaoyan He; Xiaohua Jiang; Andrew Man-Lok Chan; Lin Zou; Jianmin Sun; Hui Zhao

doi:10.1186/s13578-022-00946-9

Inhibition of PI3 kinase isoform p110α suppresses neuroblastoma growth and induces the reduction of Anaplastic Lymphoma Kinase

Cell Biosci. 2022 Dec 30;12(1):210. doi: 10.1186/s13578-022-00946-9.

Authors

Yue Guo¹, Donghao Guo¹, Shaoting Zhang², Yuan Zhang¹, Xiaoyan He³, Xiaohua Jiang¹, Andrew Man-Lok Chan¹, Lin Zou⁴, Jianmin Sun⁵, Hui Zhao^{6

7

8}

Affiliations

¹ Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
² NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Science and Technology Center, School of Basic Medical Sciences, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan, 750004, China.
³ Newborn Screening Center & Center for Clinical Molecular Medicine of Children's Hospital, Chongqing Medical University, Chongqing, 400014, China.
⁴ Clinical Research Unit, Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200062, China.
⁵ NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Science and Technology Center, School of Basic Medical Sciences, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan, 750004, China. jianmin.sun@nxmu.edu.cn.
⁶ Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. zhaohui@cuhk.edu.hk.
⁷ Kunming Institute of Zoology Chinese Academy of Sciences - The Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Hong Kong, SAR, China. zhaohui@cuhk.edu.hk.
⁸ Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics, The Chinese University of Hong Kong, Hong Kong, SAR, China. zhaohui@cuhk.edu.hk.

Abstract

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 p110α 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 p110α but not by p110β or p110δ. Suppression of p110α inhibited the growth of neuroblastoma cells both in vitro and in vivo, suggesting a crucial role of p110α in the tumorigenesis of neuroblastoma. Mechanistically, inhibition of p110α 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 p110α in the tumorigenesis of neuroblastoma, and strongly suggest the p110α inhibitors as potential drugs in treating neuroblastoma.

Keywords: ALK; Alpelisib; Neuroblastoma; PI3 Kinase; PIK3CA; p110α.

Abstract

Grants and funding