EDEM1 Inhibits Endoplasmic Reticulum Stress to Induce Doxorubicin Resistance through Accelerating ERAD and Activating Keap1/Nrf2 Antioxidant Pathway in Triple-Negative Breast Cancer.

ABSTRACT: Doxorubicin (DOX)-based chemotherapy is the basic treatment for triple-negative breast cancer (TNBC). However, chemoresistance is still one of the major causes of metastasis, recurrence, and poor outcomes. Recently, a close relationship between chemoresistance and endoplasmic reticulum (ER) stress has been found. In this study, ER-associated degradation (ERAD)-related protein EDEM1 (ER degradation enhancing α-mannosidase-like 1) plays a vital role in DOX-induced ER stress, which is up-regulated in tumor cells and tissues. In vitro and in vivo experiments reveal the promoting role of EDEM1 in the progression and chemoresistance of TNBC. Besides, EDEM1 attenuates autophagy and reduces ER stress-related apoptosis, indicating its inhibitory effect on ER stress. Furthermore, EDEM1 promotes ERAD

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12305169 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature