Breast cancer plasticity is restricted by a LATS1-NCOR1 repressive axis

Abstract

Breast cancer, the most frequent cancer in women, is generally classified into several distinct histological and molecular subtypes. However, single-cell technologies have revealed remarkable cellular and functional heterogeneity across subtypes and even within individual breast tumors. Much of this heterogeneity is attributable to dynamic alterations in the epigenetic landscape of the cancer cells, which promote phenotypic plasticity. Such plasticity, including transition from luminal to basal-like cell identity, can promote disease aggressiveness. We now report that the tumor suppressor LATS1, whose expression is often downregulated in human breast cancer, helps maintain luminal breast cancer cell identity by reducing the chromatin accessibility of genes that are characteristic of a “basal-like” state, preventing their spurious activation. This is achieved via interaction of LATS1 with the NCOR1 nuclear corepressor and recruitment of HDAC1, driving histone H3K27 deacetylation near NCOR1-repressed “basal-like” genes. Consequently, decreased expression of LATS1 elevates the expression of such genes and facilitates slippage towards a more basal-like phenotypic identity. We propose that by enforcing rigorous silencing of repressed genes, the LATS1-NCOR1 axis maintains luminal cell identity and restricts breast cancer progression.

Real-time fluorescence imaging flow cytometry enabled by motion deblurring and deep learning algorithms

“…[1][2][3] This innovative technology combines the advantages of flow cytometry and fluorescence microscopy, enabling the acquisition of highresolution cell images with high throughput in a continuous flow mode. 4 The versatility of IFC has been demonstrated in a number of biological and medical fields, such as pathology, [5][6][7][8] immunology, [9][10][11] microbiology, [12][13][14] cancer treatment, [15][16][17][18] and molecular biology. [19][20][21][22] Real-time cell classification is a critical function of IFC, particularly for larger-scale single-cell sorting and analysis.…”

Subtype Transdifferentiation in Human Cancer: The Power of Tissue Plasticity in Tumor Progression

“…This is achieved via interaction of LATS1 with the Nuclear Core Repressive complex 1 (NCOR1) and recruitment of HDAC1, driving histone H3K27 deacetylation near NCOR1-repressed basal-like genes. Consequently, decreased expression of LATS1 elevates the expression of such genes and facilitates slippage towards a more basal-like phenotypic identity [17].…”

STRIPAK Dependent and Independent Phosphorylation of the SIN Kinase DBF2 Controls Fruiting Body Development and Cytokinesis during Septation and Ascospore Formation in Sordaria macrospora

“…The Hippo pathway is known for its crucial roles in regulating cell proliferation and promoting apoptosis during cellular differentiation. Overexpression of the LATS1 gene induces G2-M phase arrest and reduces the ability of breast cancer cells to form tumours [ 30 , 31 , 32 ]. The growing evidence highlighting the role of Hippo signalling in cancer biology indicates that targeting this pathway could provide new possibilities for alternative therapeutics [ 33 ].…”