Integrin ß8 facilitates tumor growth and drug resistance through a Y-box binding protein 1-dependent signaling pathway in bladder cancer.

ABSTRACT

The transmembrane receptors integrins are the bridges for cell-cell or cell-ECM interaction, which is strictly correlated to cancer development in several tumor types. Here, we revealed that integrin ß8 serves as a driver to mediate sustained growth of bladder cancer and development of drug resistance. The elevated expression of integrin ß8 was observed in highly malignant bladder tumor tissues from patients. The in vitro and in vivo results further indicated that integrin ß8 overexpression in Biu87/T24 bladder cancer could mediate and strengthen cell proliferation and resistance to mitomycin C and hydroxycamptothecin. Mechanistically, integrin ß8 on the cellular surface might recruit phosphorylated Y-box binding protein 1, leading to the activation of c-Myc and nuclear factor-κB signals. Pharmacological targeting of integrin ß8 by Arg-Gly-Asp-Ser efficiently suppressed sustained growth and drug resistance in bladder cancer cells. Our findings identified integrin ß8 as a marker of bladder cancer diagnosis and development, and provides an innovative approach for clinical bladder cancer therapy.