The Purinergic Ligand-Gated Ion Channel 7 Receptor Promotes the Proliferation, Invasion, and Migration of Breast Cancer Cells

Abstract

Purinergic ligand-gated ion channel 7 receptor (P2X7R) has essential functions in tumor proliferation, apoptosis, metastasis, and invasion, and the purpose of this study was to explore the effects of P2X7R on the biological behaviors of MCF-7 and MDA-MB-231 cells. A bioinformatics analysis of P2X7R expression in breast cancer was performed and its relationships with overall survival and immune cell infiltration were determined. P2X7R ion channel function was detected via a Fluo-4-AM assay. Proliferation, migration and invasion were investigated using CCK-8, scratch wound healing, and Transwell assays, respectively. The levels of P2X7R, JNK, p-JNK, Akt, p-Akt, E-cadherin, N-cadherin, vimentin and GAPDH were detected by western blotting. The role of P2X7R on the biological behaviors of MCF-7 cells was detected in vivo. Bioinformatics analysis revealed an obvious increase in the expression of P2X7R in breast cancer and differences were observed among the different subtypes. High expression of P2X7R was negatively correlated with overall survival and affected immune cell infiltration. The experimental results revealed that both types of cells express functional P2X7R. ATP and BzATP can promote proliferation, invasion, and metastasis after P2X7R activation; upregulate p-Akt, p-JNK, N-cadherin and vimentin; and downregulate E-cadherin compared with the control group, and the addition of the antagonist A438079 or oxATP or the knockdown of P2X7R could weaken these effects. The activation of P2X7R in breast cancer cells can promote their biological behaviors, indicating that P2X7R is a latent therapeutic target in breast cancer.