RT Journal Article SR Electronic T1 Targeting the Unfolded Protein Response as a Potential Therapeutic Strategy in Renal Carcinoma Cells Exposed to Cyclosporine A JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 1049 OP 1057 VO 37 IS 3 A1 SANDRA BODEAU A1 CHLOÉ SAUZAY A1 RÉMY NYGA A1 CHRISTOPHE LOUANDRE A1 VÉRONIQUE DESCAMPS A1 CATHERINE FRANÇOIS A1 CORINNE GODIN A1 GABRIEL CHOUKROUN A1 ANTOINE GALMICHE YR 2017 UL http://ar.iiarjournals.org/content/37/3/1049.abstract AB Background/Aim: Organ transplant patients treated with the immunosuppressive drug cyclosporine A often present malignant kidney tumors. Cyclosporine A can promote oncogenesis in a cell-intrinsic manner by increasing the production of vascular endothelial growth factor (VEGF). Materials and Methods: We explored the impact of cyclosporine A and the role of the unfolded protein response (UPR) on three human renal cell carcinoma (RCC) cell lines under normoxic and hypoxic (1% O2) conditions. Results: Cyclosporine A regulated the expression of VEGF at the post-transcriptional level. Cyclosporine A induced the inositol requiring enzyme-1α (IRE1α) arm of the UPR and stabilized neosynthesized proteins in RCC cells. Toyocamycin, an inhibitor of IRE1α, abolished the clonogenic growth of RCC cells and reduced induction of VEGF by cyclosporine A under hypoxia. Conclusion: Our findings highlight the impact of cyclosporine A on the proteostasis of RCC cells, and suggest the potential therapeutic interest of targeting the UPR against tumors arising in the context of organ transplantation.