GRP78 inhibition enhances ATF4-induced cell death by the deubiquitination and stabilization of CHOP in human osteosarcoma

New targeted therapies are urgently needed to improve the survival of patients with refractory osteosarcoma (OS). In this study, we show that bortezomib (BTZ), not for OS treatment in the clinic, induces endoplasmic reticulum (ER) stress in U-2 OS cells. Loss of GRP78 sensitizes OS to BTZ with concomitant upregulation of ATF4 and CHOP, which indicates excessive protein synthesis. The relevance of these findings is confirmed in vivo as shown by GRP78 knockdown that delays the growth of U-2 OS xenografts in the presence of BTZ.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wHho5U
via IFTTT