From lactation to malignancy: A comparison between healthy and cancerous breast gland at single-cell resolution reveals new issues for tumorigenesis

Abstract

This study, based on datasets from healthy tissues, lactating mammary epithelial cells, and breast cancer phenotypes, investigates mammary gland pathophysiology at single-cell resolution to identify key regulators in breast cancer development and to gain a deeper understanding of its biology and heterogeneity. We suggest that antileukoproteinase (SLPI) has prognostic value associated with metastasis in basal breast cancers. Our analysis highlights the similarity between triple-negative breast cancer cells and mature luminal lactocytes, which share active regulons (SOX2, MTHFD1, POU4F3, and ZNF32), suggesting conserved molecular mechanisms. Among the differences, the absence of MALAT1 and NEAT1 lncRNAs in lactocytes correlates with loss of six transcription factors (EP300, ELF1, E2F3, BDP1, HOXC10, and KLF6). These findings provide insights into breast cancer and suggest new therapeutic targets.