Myoepithelial cells in mammary development and ductal carcinoma: a Sphinx-like riddle

Myoepithelial cells (MECs) are vital components of the mammary gland and coordinate critical interactions between the ductal epithelium and the basement membrane. Recent studies have significantly enhanced our understanding of the role of MECs in breast ductal carcinoma. In normal mammary tissue, MECs provide a natural defense barrier by maintaining ductal architecture, basement membrane integrity, and epithelial polarity. They can also suppress tumor expansion through paracrine signaling and direct regulation of the tumor microenvironment. Furthermore, MECs show a “Sphinx-like” duality, as they may acquire a pro-tumorigenic phenotype under specific pathological conditions. Nevertheless, critical knowledge gaps regarding this functional paradox remain, including the mechanisms regulating chemokines such as CXCL12 and CXCL14, as well as alterations in matrix metalloproteinases (MMPs). To better define the potential of targeting MECs for controlling cancer cell invasion, further studies are needed to clarify how specific MEC phenotypes change during the transition from atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). In this Review, we summarize the paradoxical roles of MECs in normal mammary tissue and breast ductal carcinoma and discuss their potential value for identifying novel therapeutic targets in breast cancer biology.