Postponed: Targeting RSK4 prevents both chemoresistance and metastasis in lung and bladder cancer

This event has been postponed. We hope to arrange a new date for it in due course.

 Lung and bladder cancers are aggressive and fast spreading form of cancer with unmet clinical needs.

We have identified RSK4, a member of the p90 ribosomal S6 kinases (RSKs) family, as a promoter of drug resistance and metastasis in lung and bladder cancer cells, and silencing this kinase sensitises to therapy and hinders metastasis in vitro and in vivo. We have determined the crystal structures of RSK4 in both its inactive and active states, revealing differences from those seen previously for other AGC kinases. We have shown that the βB­sheet, a unique structural feature of RSKs and MSKs, plays a key role in RSK4 regulation and activation.

Finally, drug screening revealed several floxacin antibiotics as potent RSK4 activation inhibitors, and trovafloxacin reproduces all effects of RSK4 silencing.

Through crystallography and Markov transient analysis, we have proposed a mechanism for the action of this compound. Hence, we suggest that RSK4 inhibition represents a novel therapeutic strategy for treating lung and bladder cancers.