Mortalin (GRP75/HSPA9) upregulation promotes survival and proliferation of medullary thyroid carcinoma cells.

ABSTRACT: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the rearranged during transfection (RET) proto-oncogene. For therapy of advanced MTC, the Food and Drug Administration recently approved vandetanib and cabozantinib, the tyrosine kinase inhibitors targeting RET, vascular endothelial growth factor receptor, epidermal growth factor receptor and/or c-MET. Nevertheless, not all patients respond to these drugs, demanding additional therapeutic strategies. We found that mortalin (HSPA9/GRP75), a member of HSP70 family, is upregulated in human MTC tissues and that its depletion robustly induces cell death and growth arrest in MTC cell lines in culture and in mouse xenografts. These effects were accompanied by substantial downregulation of RET, induction of t

SUBMITTER: Starenki D 

PROVIDER: S-EPMC4451452 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature