Abstract A047: Gamma Aminobutyric Acid Subunit Pi (GABRP) Promotes Breast Cancer Metastasis to the Brain

Abstract

Abstract Triple negative breast cancer (TNBC) is an aggressive subset of breast cancer associated with poor prognosis. Although TNBC is only responsible for about 10-15% of breast cancer cases, it accounts for nearly 37% of mortalities. A main factor resulting in this poor prognosis is a higher risk of rapid relapse, which is distant metastasis or death within two years of diagnosis, compared to other breast cancer subsets. To begin to tease out mechanisms of this TNBC-specific rapid relapse, we analyzed differential expression between those tumors resulting in rapid relapse versus those tumors with delayed relapse. This analysis was completed in two independent microarray datasets and revealed a significant upregulation of gamma aminobutyric acid subunit pi (GABRP) mRNA in the TNBC tumors that rapidly relapsed. Previous work by us and others has revealed GABRP as a driver of aggressive behaviors in TNBC cell lines; however, its role in metastatic recurrence is still unclear. We have also observed a correlation between high GABRP mRNA and preferential metastatic progression to the brain. Thus, we hypothesized GABRP is a key mediator of metastasis in aggressive TNBCs, specifically in the establishment of brain metastases. To date, we have completed preliminary in vivo experimental metastasis studies of human breast cancer cells with and without GABRP expression where loss of GABRP reduces brain metastasis. Ongoing studies aim to test metastatic progression in a spontaneous metastasis in vivo model. We are also optimizing an antibody for biomarker screening in patients. Combined, our studies provide strong evidence that GABRP is a major driver of brain-specific metastases and subsequent poorer outcomes associated with TNBC, suggesting targeting GABRP has high therapeutic potential to reduce metastasis and mortality in TNBC patients. Citation Format: Rebecca Packard. Gamma Aminobutyric Acid Subunit Pi (GABRP) Promotes Breast Cancer Metastasis to the Brain [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A047.