Deguelin attenuates non-small cell lung cancer cell metastasis through inhibiting the CtsZ/FAK signaling pathway.

Lung cancer is the leading cause of cancer-related death among both men and women every year, mainly due to metastasis. Although natural compound deguelin has been reported to inhibited cell migration and invasion in various cancer cells, the details of this regulation progress remain to be fully elucidated. In this study, we investigated the underlying mechanism of deguelin-suppressed metastasis of non-small cell lung cancer (NSCLC) cells. Our results demonstrate that deguelin inhibits NSCLC cell migration, invasion, and metastasis both in vitro and in vivo. These inhibitory effects of deguelin were mediated by suppressing of Cathepsin Z (CtsZ) expression and interrupting the interaction of CtsZ with integrin β3. Moreover, deguelin inhibits the activation of CtsZ downstream FAK/Src/Paxillin signaling. Knockdown of CtsZ mimicked the effect of deguelin on NSCLC cells migration and invasion. Our study reveals that deguelin exerts its anti-metastatic effect both in vitro and in vivo is partly dependent on the suppression of CtsZ signaling. Deguelin would be a potential anti-metastasis agent against NSCLC.