Repurposed floxacins targeting RSK4 prevent chemoresistance and metastasis in lung and bladder cancer.

ABSTRACT: Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells. Silencing this kinase, through either RNA interference or CRISPR, sensitized tumor cells to chemotherapy and hindered metastasis in vitro and in vivo in a tail vein injection model. Drug screening revealed several floxacin antibiotics as potent RSK4 activation inhibitors, and trovafloxacin reproduced all effects of RSK4 silencing in vitro and in/ex vivo using lung cancer xenograft and genetically engineered mouse models and bladder tumor explants. Through

SUBMITTER: Chrysostomou S 

PROVIDER: S-EPMC7611705 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature