Accession Number : ADA598785


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


Descriptive Note : Final rept. 15 May 2010-14 May 2013


Corporate Author : WAYNE STATE UNIV DETROIT MI


Personal Author(s) : Zhang, Kezhong ; Yang, Zeng-Quan


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a598785.pdf


Report Date : Jun 2013


Pagination or Media Count : 95


Abstract : 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.


Descriptors :   *BREAST CANCER , CELLS(BIOLOGY) , CYTOPLASM , DEATH , DEGRADATION , GENES , GENOME , INTERACTIONS , LIPIDS , MAINTENANCE , MEDICAL RESEARCH , MEMBRANES , MODULATION , MOLECULES , ONCOGENIC VIRUSES , PROTEINS , RETICULAR FORMATION , TARGETING


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE