A novel USP9X substrate TTK contributes to tumorigenesis in non-small cell lung cancer

ABSTRACT: The X-linked deubiquitinase, USP9X, is implicated in multiple cancers by targeting various substrates. Increased expression of USP9X is observed in non-small cell lung cancer (NSCLC) and is correlated with poor prognosis. However, the molecular mechanism for USP9X regulating tumor cell survival and tumorigenesis in NSCLC is less defined. In this study, chemical labeling quantitative proteomic screening was applied to analyze A549 cells with or without USP9X RNA interference, and the resulting data suggested that TTK is a potential substrate of USP9X. Further experimental evidences confirmed that USP9X stabilized TTK via direct interaction and deubiquitination of TTK. Moreover, knockdown of USP9X or TTK inhibited cell proliferation, migration and tumorigenesis, and the immunohistochemical analysis of clinical NSCLC samples showed that the protein expression levels of USP9X and TTK were significantly elevated and positively correlated in tumor tissues. In summary, our data demonstrated that the USP9X-TTK axis may play a critical role in NSCLC, and could be considered as the potential therapeutic target.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell Of Lung

DISEASE(S): Non-small Cell Lung Carcinoma

SUBMITTER: Jing Gao  

LAB HEAD: Zhou Hu

PROVIDER: PXD007726 | Pride | 2018-05-07

REPOSITORIES: Pride