Endoplasmic Reticulum-Associated Degradation Factor ERLIN2: Oncogenic Roles and Molecular Targeting of Breast Cancer.

摘要

Previous genomic analysis has led us to identify the endoplasmic reticulum (ER) lipid raftassociated 2 (ERLIN2) gene as one of the candidate oncogenes within the 8p11-12 amplicon in a subset of aggressive breast cancer. We proposed that ERLIN2, an ER membrane protein, plays an unconventional oncogenic role through the endoplasmic reticulum (ER) stress pathway. In this study, we found: (1) ERLIN2 is required for cell proliferation and maintenance of transforming phenotypes in aggressive, ERLIN2-amplified breast cancer; (2) the UPR pathway, through the IRE1 /XBP1 axis, modulated the high-level expression of the ERLIN2 protein; (3) ERLIN2 also plays a key role in maintaining lipogenic phenotype of breast cancer cells by regulating activation of Sterol Regulatory Element-Binding Protein 1c (SREBP1c), the key lipogenic trans-activator; (4) ERLIN2 regulates activation of SREBP1c by interacting with Insulin-induced Gene 1 (INSIG1); (5) ERLIN2 had the ability to protect breast cancer cells from ER stress-induced cell death. The information provided here sheds new light on the mechanism of the novel ER factor ERLIN2 in promoting breast cancer progression.