A Breakthrough In Extracellular ATP-Driven Invasion Process

Hui Yang, Yue-Hang Geng, Pe

Abstract

Recently, an original article titled “Extracellular ATP promotes breast cancer invasion and epithelial-mesenchymal transition via hypoxia-inducible factor 2α signaling” was published in Cancer Science [1]. In this article, we firstly demonstrated that extracellular ATP could up-regulate both HIF-1/2α and HIF signaling related genes even under normoxia conditions. Further, using transwell invasion assay, we demonstrated that it was HIF-2α that mediated ATP-driven invasion. In addition, we illustrated that ATP could regulate HIF-2α via P2Y2-AKT-PGK1 pathway, provoking HIF-2α target genes, through which LOXL2 and MMP-9 mediated ATP-driven invasion, and E-cadherin and Snail mediated ATP‐induced epithelial‐mesenchymal transition (EMT). We also demonstrated the function of HIF-2α in promoting tumor growth and metastasis via xenograft model. Moreover, molecules involved in ATP-HIF signaling were associated with clinical breast cancer progression, indicating that the ATP-HIF signaling might be a potential target for breast cancer therapy.