Abstract 200: OA inhibits the development of breast cancer through K1108 acetylation of Zeb1

Abstract Background:Olive oil has long been considered a healthier edible oil, rich in 75% oleic acid (OA) as its main component. OA is a monounsaturated fatty acid, and recent studies have shown that it is no longer limited to protecting cardiovascular and cerebrovascular systems, but can also reduce the risk of cancer. However, there is limited research on the specific mechanism. After fatty acid is ingested into the body, through fatty acids β-oxidation produces acetyl-CoA, which is a donor of protein acetylation. EMT is an important process to regulate tumor metastasis, and Zeb1 is one of the important EMT transcription factors. Therefore, we explored whether OA could inhibit the progress of breast cancer by affecting the acetylation modification of Zeb1. Methods: Western blotting, CCK8 assay, and Transwell were used to test the impact of gradient doses of OA on breast cancer cells. Immunoprecipitation and Immunoprecipitation mass spectrum were used to determine the acetylation modification sites of Zeb1. Coimmunoprecipitation, IF, and pull-down were used to test and verify the acetylase and deacetylase of Zeb1. Knockdown endogenous ZEB1 and then reconstructed stable cell lines of Zeb1 wild-type (Zeb1K1108WT), acetylation activated (Zeb1K1108Q), and inactivated mutants (Zeb1K1108R) by lentivirus. Detection of Zeb1 acetylation in patient tissue samples and mouse models under OA treatment using Zeb1-specific acetylation-modified antibodies. Results: OA inhibits the proliferation and migration of breast cancer cells in a concentration gradient-dependent manner, and inhibits the expression of Zeb1, N Cadherin, and upregulates E Cadherin. Among numerous fatty acids, only OA can promote the acetylation of Zeb1 by adjusting the ratio of acetyl-CoA and NAD+/NADH. K1108 is a biologically functional acetylation site of Zeb1, Zeb1K1108R exerts the cancer promoting function of Zeb1, while Zeb1K1108Q does not. OA can promote acetylation of Zeb1K1108WT, but cannot promote acetylation of Zeb1K1108R. Conclusions: OA inhibits the development of breast cancer through K1108 acetylation of Zeb1. These results suggest that breast cancer may be ameliorated through dietary interventions. Citation Format: Min Guo, Yanjin Wang, Yi Shi, Shuang Yang. OA inhibits the development of breast cancer through K1108 acetylation of Zeb1 [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(6_Suppl):Abstract nr 200.