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Acidosis promotes tumorigenesis by activating AKT/NF-κB signaling

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Abstract

The microenvironment of solid tumors is often acidic due to poor vascular perfusion, regional hypoxia, and increased glycolytic activity of tumor cells. Although acidosis is harmful to most types of cells, tumor cells seem well adapted to such harsh conditions. Moreover, overwhelming evidence indicates that tumor cells are more invasive and more aggressive in acidic conditions by a cascade of cell signaling and upregulation of oncogenic gene expression. Therefore, how extracellular acidic signals are transduced to the cytoplasm and then into the nucleus is an interesting topic to many cancer researchers. In this review, we update on the recent advances in acidosis-induced tumorigenesis through the acid-sensing ion channels (ASICs) and activation of cell signaling.

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Funding

This research was supported by grants from the National Natural Science Foundation of China No. 81772575 (LY) and the key project of Health Bureau of Zhejiang Province No. 2018274734 (LY), and NIH grant R01 CA154989 (YM).

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  1. Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang, P.R. China

    Liu Yang & Xiaoge Hu

  2. Cancer Institute and Department of Pharmacology/Toxicology, University of Mississippi Medical Center, Jackson, MS, USA

    Xiaoge Hu & Yin-Yuan Mo

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  1. Liu Yang
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  2. Xiaoge Hu
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Correspondence to Yin-Yuan Mo.

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Yang, L., Hu, X. & Mo, YY. Acidosis promotes tumorigenesis by activating AKT/NF-κB signaling. Cancer Metastasis Rev 38, 179–188 (2019). https://doi.org/10.1007/s10555-019-09785-6

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