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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00320

ATP1A1 Integrates AKT and ERK Signaling via Potential Interaction with Src to Promote Growth and Survival in Glioma Stem Cells

 Shali Wang1*,  Song Chen2*,  Yang Yu1, Chen Chen2, Gang Huo2, Jinmu Deng3, Hongxin Zhao4, Rui Xu2 and Li Jiang2
  • 1Chongqing Medical University, China
  • 2Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University, China
  • 3Department of Neurosurgery, Children‘s Hospital of Chongqing Medical University, China
  • 4Department of Neurosurgery, First People’s Hospital of Zunyi, China

Abstract
Glioma stem cells (GSCs) have been considered to be responsible for treatment failure due to their self-renewal and limitless proliferative property. Recently, the Na+/K+-ATPase a1 (ATP1A1) subunit was described as a novel therapeutic target for gliomas. Interestingly, our previous proteomics study revealed that ATP1A1 is remarkably overexpressed in GSCs. In the current study, we investigated the role of ATP1A1 in regulating growth, survival, and tumorigenicity of primary human GSCs and the underlying molecular mechanism. We tested RNA and protein expression of ATP1A1 in glioma tissues and GSCs. In addition, we knocked down ATP1A1 in GSCs and assessed the effects thereof on growth, survival, and apoptosis. The role of ATP1A1 in signaling pathways was investigated in vitro. We found that the ATP1A1 expression level was associated with the grade of glioma. Knockdown of ATP1A1 in GSCs in vitro inhibited cell proliferation and survival, increased apoptosis, and halted cell-cycle progression at the G1 phase. Cell proliferation and survival were resumed upon rescue of ATP1A1 expression in ATP1A1-knockdown GSCs. The ERK1/2 and AKT pathways were inhibited through suppression of Src phosphorylation by ATP1A1 knockdown. Collectively, our findings suggest that ATP1A1 overexpression promotes GSC growth and proliferation by affecting Src phosphorylation to activate the ERK1/2 and AKT signaling pathways.

Keywords: ATP1A1, glioma stem cells, Proliferation and survival, ERK/Akt, src

Received: 11 Sep 2018; Accepted: 09 Apr 2019.

Edited by:

Giorgio Seano, Institut Curie, France

Reviewed by:

Shwetal Mehta, Barrow Neurological Institute (BNI), United States
Elisabetta Stanzani, Humanitas Research Hospital, Italy  

Copyright: © 2019 Wang, Chen, Yu, Chen, Huo, Deng, Zhao, Xu and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Shali Wang, Chongqing Medical University, Chongqing, China, 63557408@qq.com
Dr. Song Chen, Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, China, chensong198125@126.com