Toxicological effects of bisphenol A exposure-induced cancer cells migration via activating directly integrin β1

Bisphenol A (BPA) is an important chemical that widely used in our life. Mounting evidences show that BPA can leak into environment, which associates with the health risks, such as initiation and metastasis of cancer, but the mechanisms still need to be interpreted. Integrin β1 is the most known subunit in integrin family, its abnormal expression and activation are tightly linked to tumorigenesis and a number of hallmarks of cancer. Here we show that environmental concentration (10^-8 M) of BPA exposure can quickly activate integrin β1 to induce cancer cell migration, and this effect is proved as a direct interaction between BPA and integrin β1, which is independent from classical or non-canonical estrogen receptors. The data further indicates that residues S134, D137 and E229 in integrin β1 played important roles in the interaction as predicted by AutoDock Vina, and confirmed by spectroscopy and native-PAGE. The study is the first to show a tumorigenic mechanism of BPA on tumor metastasis by the direct activation of integrin β1 molecule, and give rise to profound concerns about widespread use of BPA in the manufacture of plastics and human health.