Overexpression of α2 subunit of Na-K-ATPase suppresses invasion and migration of human breast cancer cells in vitro by inhibiting the Src/PI3K/Akt signaling pathway

Abstract

Objective To investigate the expression of α2 subunit of Na-K-ATPase (ATP1A2) in human breast cancer and the effects of ATP1A2 overexpression on the invasion and migration of breast cancer cells in vitro. Methods Based on the data from the Cancer Genome Atlas (TCGA) database, the differences of ATP1A2 expression were analyzed between normal breast tissue and breast cancer tissue and between breast cancer patients with and without distal metastasis. The breast cancer MDA-MB-231 and SK-BR-3 cells transfected with pEZ-M35-ATP1A2 plasmid for ATP1A2 overexpression were evaluated for invasion and migration abilities using wound healing test and Transwell invasion and migration tests; The activation of Src, PI3K and Akt proteins in the transfected cells was detected with Western blotting. Results The expression of ATP1A2 was significantly lower in breast cancer tissues than in normal breast tissues, and was also lower in patients with than in those without distal metastasis. In wound healing test and Transwell invasion and migration tests, the breast cancer cells with ATP1A2 overexpression showed significantly lowered invasion and migration abilities as compared with the control cells. Western blotting showed that ATP1A2 overexpression significantly reduced the phosphorylation levels of Src, PI3K and Akt proteins in the breast cancer cells. Conclusion ATP1A2 is lowly expressed in human breast cancer tissues and shows a likely correlation with distal metastasis. Overexpression of ATP1A2 can significantly inhibit the invasion and migration of breast cancer cells in vitro possibly by inhibiting the Src/PI3K/Akt signaling pathway.

Keywords

• breast cancer
• cell invasion
• cell migration
• α2 subunit of na-k-atpase
• src/pi3k/akt signaling pathway