Integrin β8 facilitates tumor growth and drug resistance through a Y‐box binding protein 1‐dependent signaling pathway in bladder cancer

Abstract

Transmembrane receptors integrins are the bridges for cell‐cell or cell‐extracellular matrix interaction, which is strictly correlated to the cancer development in several tumor types. Here, we revealed that integrinβ8 serves as driver to mediate bladder cancer sustained growth and drugs resistance development. The elevated expression of integrin β8 was observed in high malignant bladder tumor tissues from patients. The in vitro and in vivo results further demonstrated that integrin β8 overexpression in Biu87/T24 bladder cancer could mediate strengthen cells proliferation and resistance to mitomycin C and hydroxycamptothecin. Mechanistically, integrin β8 on cellular surface might recruit the phosphorylated YBX1, leading to the activation of c‐Myc and NF‐kB signals. Pharmacological targeting of integrin β8 by Arg‐Gly‐Asp‐Ser efficiently suppressed the sustained growth and drugs resistance in bladder cancer cells. Our findings identified integrin β8 as a marker of bladder cancer diagnosis and development, and provides an innovative approach for clinic bladder cancer therapy.