Unraveling myoepithelial cell plasticity in breast cancer: a transcriptomic approach

Myoepithelial cells (MECs) are integral to mammary gland physiology, classically serving a structural and tumor-suppressive role. While their function in normal breast tissue and ductal carcinoma in situ is well characterized, their behavior in human invasive breast cancer has not been previously examined. In this study, we performed a comprehensive transcriptomic analysis of MECs isolated from seven archived human breast cancer specimens, directly comparing them with MECs from adjacent normal tissue to define gene expression changes associated with invasive progression. The analysis revealed marked transcriptomic reprogramming across three key domains: extracellular matrix (ECM) interactions, epithelial-mesenchymal transition (EMT), and cellular signaling. Notable findings include stromal remodeling characterized by overexpression of 17 distinct collagen genes; compromise of the basement membrane through upregulation of matrix metalloproteinases (MMPs 2, 9, 11, and 14); and dysregulation of epithelial markers (KRT5, KRT7, KRT14), consistent with a phenotypic shift toward a cancer-associated fibroblast (CAF)-like state. In addition, increased expression of pro-tumorigenic mediators such as SPARC, POSTN, and integrin subunits was observed. Despite the limited sample size, these results indicate substantial molecular plasticity in MECs, suggesting a transition from a tumor-suppressive to a tumor-promoting phenotype during invasive disease. Overall, this study identifies a fundamental shift in myoepithelial identity and provides a critical framework for future investigations into the role of MEC plasticity in driving breast cancer progression.