Abstract 1711: SLC6A15, a novel potential metabolic target for non-small cell lung cancer

Abstract

Abstract Current therapeutic targets for non-small cell lung cancer consist only of signaling pathways targeting VEGF, EGFR or ALK. Recent researches have put focus on understanding cancer metabolism (such as 2-hydroxyglutarate accumulation in gliomas with mutant IDH1) and have opened a new avenue in cancer therapeutics which can complement the current practices. Here we introduce a new potential metabolic target for non-small cell lung cancer, SLC6A15. It is a trans-membrane protein known to facilitate uptake of branched chain amino acids (BCAA) (leucine, isoleucine and valine) and proline into the cells. BCAA was recently reported to increase cellular proliferation by regulating m-TOR in normal cells like beta-pancreatic cells. Here we show that these BCAA are highly enriched in lung tumor cell lines (H1299 & H460) as well as in human lung tumor tissues as a result of overexpression of SLC6A15. We performed a transient knockdown of this transporter using siRNA for SLC6A15 and observed its effect on reduced clonogenicity of the two cancer cell lines by 3.3 and 1.6 fold, respectively. Further, gas chromatography mass spectrometry (GC-MS) analysis of the cells treated with si(SLC6A15) revealed selective reduction of BCAA levels by 1.3 to 1.5 fold but not in Proline, which can be synthesized in the cells unlike BCAA. These results support the role of these amino acids in tumor cell proliferation. Overexpression of SLC6A15 protein was confirmed by western blot analysis in 8 NSCLC cell lines and is indicative of its tumor specific nature. This finding is also supported by SLC6A15 gene expression data available on TCGA (The Cancer Genome Atlas), where 6 out of 10 patients show high expression of this gene. Therefore, we conclude that SLC6A15 is a new candidate of therapeutic target for NSCLC. Targeted inhibition may open new possibilities to specific reduction of tumor cell proliferation and possibly, increase life expectancy of patients suffering from NSCLC. Citation Format: PALLEVI SRIVASTVA, Hyuntae Yoo. SLC6A15, a novel potential metabolic target for non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1711. doi:10.1158/1538-7445.AM2015-1711