Deubiquitinase JOSD1 promotes tumor progression via stabilizing Snail in lung adenocarcinoma.

Accumulating evidence suggests that the deubiquitinase JOSD1 accounts for aggressiveness and unfavorable prognosis in multiple human cancers. But, the significance of JOSD1 in lung adenocarcinoma (LUAD) is elusive. We established that JOSD1 was aberrantly overexpressed in LUAD tissues, relative to normal tissues. Elevated JOSD1 levels in LUAD tissues positively related to advanced clinicopathological characteristics and poor overall survival (OS) in LUAD patients. Furthermore, we found that JOSD1 knockdown suppressed tumor cell proliferation and metastasis, whereas overexpression of JOSD1 led to opposite phenotypes. Mechanistically, JOSD1 stabilized Snail protein through deubiquitination, which promotes the epithelial-to-mesenchymal transition (EMT) process. Indeed, JOSD1 promoted tumor cell invasion as well as metastasis on the dependence of Snail. The protein expression analysis of LUAD tissues indicated that JOSD1 positively correlated with Snail. Moreover, JOSD1 and Snail co-overexpression had the worst prognosis in LUAD patients. Overall, these results demonstrated that JOSD1 was significantly overexpressed in LUAD and stabilized Snail via deubiquitination to promote LUAD metastasis.