KY216-tubulin complex captures VASH2 to inhibit NSCLC metastasis.

ABSTRACT: Metastasis significantly impacts the mortality rate of non-small cell lung cancer (NSCLC) patients. Numerous microtubule-targeting agents (MTAs) reveal anti-metastatic efficacy, but the mechanism remains unclear. In this research, we employ KY216, a microtubule inhibitor, to generate a crystal in complex with αβ-tubulin, and illustrate that the KY216-tubulin combination binds vasohibin-2 (VASH2) to restrain NSCLC metastasis. Through crystal structure analysis, specific interaction sites between KY216 and curved tubulin are identified. KY216 decreases VASH2 levels, hindering the epithelial-mesenchymal transition (EMT) process in NSCLC. Moreover, the MTA enhances the binding of VASH2 to α-tubulin, prevents the activation of zinc finger E-box binding homolog 1 (ZEB1) by VASH2, promotes detyro

SUBMITTER: He XY 

PROVIDER: S-EPMC12780157 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature