Abstract 832: Breast cancer plasticity is restricted by a LATS1-NCOR1 repressive function

Abstract

Abstract Purpose of study: Understanding the epigenetic mechanism underlying luminal-to-basal plasticity of breast cancer subtypes Experimental procedures: Epigenetic focused CyTOF, ATAC-seq, RNA-seq, FACS-sorting, Proximity Ligation Assay, orthotopic syngeneic injections of tumor cells to mouse mammary gland, and others. Summary: Breast cancer is the most frequent cancer in women. It is defined by specific types of tumors that are classified into distinct histological and molecular subtypes. However, lately, with the advent of single-cell technologies, the extent of cellular and functional intratumoral heterogeneity within breast cancer subtypes is being appreciated. Much of this heterogeneity, including transitions of luminal-to-basal cell identity, can be attributed to alterations in the activity of chromatin remodelers. The transcriptional corepressor, NCOR1, and the tumor suppressor, LATS1, are downregulated in luminal breast cancer tumors with poor prognosis. Here, we show that LATS1 impedes the emergence of an epigenetically distinct basal-like population in luminal B tumors by augmenting NCOR1 repressive activity and facilitating deacetylation of H3K27ac. Conclusion: Rigorous repression of ERα-repressed genes facilitated by LATS1-NCOR1 maintains luminal cell identity and restricts progression of luminal breast cancer. Citation Format: Yael Aylon, Noa Furth, Giuseppe Mallel, Nishanth Nataraj, Gilgi Friedlander, Ori Hassan, Rawan Zoabi, Benjamin Cohen, Tomer Salame, Saptaparna Mukherjee, Randy Johnson, Efrat Shema, Moshe Oren. Breast cancer plasticity is restricted by a LATS1-NCOR1 repressive function [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 832.