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 beta 1 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 beta 1 to induce cancer cell migration, and this effect is proved as a direct interaction between BPA and integrin beta 1, which is independent from classical or non-canonical estrogen receptors. The data further indicates that residues S134, D137 and E229 in integrin beta 1 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 beta 1 molecule, and give rise to profound concerns about widespread use of BPA in the manufacture of plastics and human health. (C) 2018 Elsevier Ltd. All rights reserved.