Abstract 6993: SLC1A4 is associated with metabolic reprogramming in triple-negative breast cancer

Abstract The solute carrier protein (SLC) family is transporters as integral membrane proteins that transport solutes in an ATP-independent manner. The SLC1 family consists of five high-affinity glutamate transporters and two neutral amino acid transporters, among which SLC1A4 transports the neutral amino acids and is known to participate in various biological processes, including metabolism and tumorigenesis. However, the relationship between SLC1A4 and breast cancer remains unclear. Here, we aimed to verify the role of SLC1A4 in triple-negative breast cancer (TNBC). To reveal the characteristics of SLC1A4 in TNBC cell lines, five cell lines (HCC38/OE, HCC1395/OE, HCC1937/OE, MDA-MB-468/KD, and Hs578T/KD) that regulate gene expression of SLC1A4 were established using a lentiviral system. The two major energy-producing pathways, glycolysis and oxidative phosphorylation, were measured according to SLC1A4 gene expression. In addition, cell proliferation, cell migration, and cell invasion ability were confirmed upon overexpression or knock-down of SLC1A4. To confirm cancer stem cell function according to SLC1A4 gene expression, ALDH activity and sphere formation ability were evaluated. To ensure transcript changes due to SLC1A4 expression, RNA sequencing was performed. Anti-cancer drug (cisplatin, carboplatin, paclitaxel, and doxorubicin) sensitivity was also tested. The result showed that energy production efficiency was significantly reduced in cells where SLC1A4 expression was suppressed. In addition, in cells overexpressing the SLC1A4 gene, the presence of SLC1A4 was confirmed to increase cell proliferation, migration, and invasion ability significantly. Transcriptome analysis results showed notable changes in genes related to signaling receptor binding. Regarding material transport, to investigate whether there was a change in amino acid uptake ability according to SLC1A4 gene expression, no difference was observed. In the drug responses, doxorubicin showed a significant sensitive response in the absence of SLC1A4 gene expression. Taken together, SLC1A4 is a potential oncogene that not only induces rapid proliferation, aggressive invasion, and migration through metabolic reprogramming but also contributes to increasing cancer stem cell capabilities. In addition, it shows the sensitive response to ADR when SLC1A4 is low or absent, so it can be used as a treatment strategy for TNBC. Citation Format: Soo Young Park, Da Sol Kim, Hayeon Kim, Min Ji Song, Han Suk Ryu. SLC1A4 is associated with metabolic reprogramming in triple-negative breast cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 6993.