biostudies-literatureLiang HBreast Cancer Research Foundation (BCRF)Breast Cancer Research FoundationU.S. Department of Health &amp; Human Services | NIH | National Cancer InstituteNCI NIH HHS986-1002https://www.ebi.ac.uk/biostudies/studies/S-EPMC12480652biostudies-literatureUnknown133(7)<h4>Background</h4>The hybrid EMT state is a key driver of tumour regenerative and metastatic potential; however, the mechanism whereby this programme regulates tumour stemness with respect to self-renewal and differentiation remains unclear.<h4>Methods</h4>We isolated epithelial/mesenchymal (E/M) (CD104^highCD44^high) and mesenchymal (M) (CD104^low CD44^high) subpopulations from basal-like breast cancer cell lines. These were assayed for tumour-initiating potential and organoid-forming ability, as well as for transcriptional regulators of the hybrid EMT state by RNA and ATAC-sequencing, and their regulation by the Wnt/ERK/CDK4/6 signalling pathway.<h4>Results</h4>E/M cells were endowed with organoid-forming ability as well as by tumour-initiating anBritish journal of cancerWnt/ERK/CDK4/6 activation in the partial EMT state coordinates mammary cancer stemness with self-renewal and inhibition of differentiation.PMC12480652P01 CA257885BCRF-18-066Norton LKumar VGriffen AZhang JRen ZSivalingam KLaFave LMHazan RBWang JBenard OLiang HZhang XSuyama Kde Simone Benito EfalseWnt/ERK/CDK4/6 activation in the partial EMT state coordinates mammary cancer stemness with self-renewal and inhibition of differentiation.<h4>Background</h4>The hybrid EMT state is a key driver of tumour regenerative and metastatic potential; however, the mechanism whereby this programme regulates tumour stemness with respect to self-renewal and differentiation remains unclear.<h4>Methods</h4>We isolated epithelial/mesenchymal (E/M) (CD104^highCD44^high) and mesenchymal (M) (CD104^low CD44^high) subpopulations from basal-like breast cancer cell lines. These were assayed for tumour-initiating potential and organoid-forming ability, as well as for transcriptional regulators of the hybrid EMT state by RNA and ATAC-sequencing, and their regulation by the Wnt/ERK/CDK4/6 signalling pathway.<h4>Results</h4>E/M cells were endowed with organoid-forming ability as well as by tumour-initiating an2025-01-01T00:00:00Z2025 Oct2026-06-03T23:33:23.498Z2026-05-03T03:11:27.453ZS-EPMC124806524076466910.1038/s41416-025-03074-6