Abstract 7: AGS3 depletion promotes tumorigenesis in a murine model of lung cancer

Abstract

Abstract Activator of G-protein Signaling 3 (AGS3/GPSM1) is a receptor independent activator of G-protein signaling that couples to Gα subunits of the heterotrimeric G-protein to mediate cellular functions. It was previously shown that AGS3 modulates prostate tumor development. In this study we investigate the role of AGS3 in the onset of lung cancer. To that end, we used a murine model of Lung Lewis Carcinoma (LLC) in mice deficient in AGS3 expression (AGS3-/-) relative to wild-type animals (AGS3+/+). AGS3-/- mice exhibited a significant increase in LLC tumor growth relative to AGS3+/+ mice. Immunohistochemical analysis of the tumors also revealed a significant increase in microvessels density in AGS3-/- tumors. FACS analysis of tumor infiltrating leukocytes also showed a significant decrease in lymphocyte recruitment in AGS3-/- tumor microenvironment (TME) relative to AGS3+/+ mice. The decrease leukocytes recruitment in AGS3-/- xenografts correlated with a marked decrease in chemokines expression in the TME. Taken together, these results indicate that AGS3 modulates LLC tumor development and progression. Citation Format: Timothy O. Adekoya, Nikia Smith, Ricardo M. Richardson. AGS3 depletion promotes tumorigenesis in a murine model of lung 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 7.