21P U2AF1 (S34F) mutation leads to altered global splicing patterns and dysregulation of cell cycle and mitosis

Abstract

were used. Pharmacological inhibition of HSP90 activity in these cell lines were achieved through geldanamycin and resorcinol derivatives. The response to these inhibitors at different time points was evaluated. Results: Westerns blots indicated that HSP70 and HSP90-a protein expression were increased after 17-AAG, IPI-504, STA-9090 and AUY-922 treatments. EGFR, EML4-ALK and CDK4, the oncogenic client proteins studied, were depleted by the HSP90 inhibitors in the NSCLC cell lines. The strong relationship between client driver protein dependence on Hsp90 and the sensitivity to its inhibition was demonstrated in the HCC827 and H3122 cell lines. Conclusions:The reduction of oncogenic client proteins alongside HSP70 and HSP90-a induction could be used as a validated biomarker signature of HSP90 inhibition in the cell lines studied. Future study will be focused on understanding the biological basis for the differential response to these treatments. Legal entity responsible for the study: Instituo de Biomedicina de Sevilla (IBIS) (CSIC, HUVR, Universidad de Sevilla) Funding: Fundación para la Investigación de Sevilla (FISEVI) Disclosure: All authors have declared no conflicts of interest.