Abstract PO006: The Role of Obesity-associated Allograft Inflammatory Factor-1 in Liver Cancer Cell Growth

Abstract

Abstract Introduction: Obesity is a risk factor in the development of liver cancer. The obesogenic tumor microenvironment is of particular importance in liver tumorigenesis due in part to lipid accumulation and monocyte recruitment which differentiate into pro-inflammatory macrophages. A novel macrophage-associated protein, whose role in obesity-associated liver tumorigenesis has yet to be explored, is allograft inflammatory-factor 1 (AIF-1). AIF-1 is a calcium binding inflammation response scaffold protein. Although, proliferation and migration have been studied, https://scholar.google.com/citations?view_op=view_citation&hl=en&user=AAeKZnoAAAAJ&sortby=pubdate&citation_for_view=AAeKZnoAAAAJ:8dzOF9BpDQo Cactivation of kinase pathways, cell survival, cell death, ROS production and lipogenesis have yet to be explored. AIF-1 is upregulated in both liver cancer and obese individuals. Our research objective is to determine the functional role of AIF-1 in promoting physiological processes important for liver tumorigenesis including proliferation, survival, ROS, and lipogenesis, and 2) determine the contribution of Akt and Erk in promoting this in-vitro phenotype. Methods: HepG2 and SNU-449 liver cancer cells were exposed to AIF-1 (10uM) with or without 10 μM ly294002 (PI3K inhibitor), 10 μM PD98059 (MAPK inhibitor), or 5μM NPS-2143 (calcium sensing receptor inhibitor). Cells were assessed for proliferation, ROS production, lipogenesis, cytotoxicity, and cell survival. Immunoblot analysis was used to measure phosphorylated Akt, Erk, IL-6, and NF-kB protein levels. Results: AIF-1 increased proliferation in HepG2 and SNU-449 liver cancer cells. Inhibiting Akt, and Erk signaling decreased AIF-1-induced proliferation while NPS-2143 CaSR inhibitor decreased proliferation only in HepG2 cells. AIF-1 promoted ROS production and the addition of Akt inhibitor blocked AIF-1 ROS production in both cell lines. Significant differences in lipogenesis were not observed among various treatments in HepG2 and SNU-449 cells. AIF-1 increased cell survival, cytotoxicity and phosphorylation of Akt and Erk, when compared to control. Conclusions: Obesity-associated AIF-1 increased proliferation, ROS, and survival while differential effects were observed with Akt or Erk inhibition. Citation Format: Jessie Waltenbaugh, Curissa Groll, Kelsie Raign, Ramona Price. The Role of Obesity-associated Allograft Inflammatory Factor-1 in Liver Cancer Cell Growth [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr PO006.