Endoplasmic Reticulum-Associated Degradation Factor ERLIN2: Oncogenic Roles and Molecular Targeting of Breast Cancer
Annual rept. 15 May 2012-14 May 2013
WAYNE STATE UNIV DETROIT MI
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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.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research