Abstract
This year there will be 260,00 new cases of breast cancer in the United States. Close to 40,000 women living with breast cancer, will die from the disease by the years end. However, these statistics are not evenly distributed across our citizens. Women of Western African descent are 40% more likely to die from breast cancer than their European counterparts. Although socioeconomic factors along with racism, including affordable quality health care, availability of healthy foods, wage gaps, and trustworthiness of our physicians, have a considerable role in the difference in survival, there still is a significant gap in our understanding of the contribution of biology. Therefore, biomarkers, mechanisms, and pathways connected with more aggressive biology that differ by race and genetic ancestry must be examined. The ubiquitin E3 ligase, glycoprotein 78 (GP78/AMFR) is an endoplasmic reticulum-resident protein that degrades unfolded proteins found in the cell. It also supports lipid synthesis, autophagy and targets certain proteins that cause endoplasmic reticulum stress that could result in apoptosis. We have found that GP78 is a functional biomarker for breast cancer in women. Higher levels of this gp78, detected by validated antibody, is associated with more aggressive subtypes of breast cancer (e.g., luminal B, HER2 and triple-negative breast cancer, TNBC) and is expressed at notably elevated levels in breast cancer compared to normal glands. In addition, its expression is associated with poor survival, regardless of subtype, specifically in women of Western African descent. In vivo experiments using murine syngeneic allograft models, comparing wild type and gp78 knock breast cancer cells show the gp78 is required for tumor growth. Further analysis reveals a role for gp78 lipogenesis linked to immune suppression in the tumor microenvironment. Conclusion: These observations suggest a role for gp78 in 1) tumor growth and 2) immune suppression, and implies a role for race and genetic ancestry in the association between gp78 and breast cancer survival. Therefore, corroborating a role for gp78 in both tumor growth and suppression of the tumor immune microenvironment will be an important future goal. We will validate and extend these findings in additional diverse patient populations to define the association between GP78, patient tumor biology, clinical feature, patient exposures, and other social determinants of health.
Citation Format: Myles A. Ellis. Does the ubiquitin E3 ligase glycoprotein 78 (gp78/amfr) link socioeconomic factors, race, and biology in breast cancer? [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2372.