Na/K-ATPase Y260 Phosphorylation–mediated Src Regulation in Control of Aerobic Glycolysis and Tumor Growth

Moumita Banerjee, Xiaoyu Cui, Zhichuan Li, Hui Yu, Liquan Cai, Xuelian Jia, Daheng He, Chi Wang, Tianyan Gao, Zijian Xie

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24 Scopus citations

Abstract

We report here the identification of α1 Na/K-ATPase as a major regulator of the proto-oncogene Src kinase and the role of this regulation in control of Warburg effect and tumor growth. Specifically, we discovered Y260 in α1 Na/K-ATPase as a Src-specific phosphorylation and binding site and that Y260 phosphorylation is required for Src-mediated signal transduction in response to a number of stimuli including EGF. As such, it enables a dynamic control of aerobic glycolysis. However, such regulation appears to be lost or attenuated in human cancers as the expression of Na/K-ATPase α1 was significantly decreased in prostate, breast and kidney cancers, and further reduced in corresponding metastatic lesions in patient samples. Consistently, knockdown of α1 Na/K-ATPase led to a further increase in lactate production and the growth of tumor xenograft. These findings suggest that α1 Na/K-ATPase works as a tumor suppressor and that a loss of Na/K-ATPase-mediated Src regulation may lead to Warburg phenotype in cancer.

Original languageEnglish
Article number12322
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Publisher Copyright:
© 2018, The Author(s).

ASJC Scopus subject areas

  • General

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