Search

Ductal carcinoma in situ (DCIS) is a pre-invasive stage of breast cancer. During invasion, the encapsulating DCIS basement membrane (BM) is compromised, and tumor cells invade the surrounding stroma. The mechanisms that regulate functional epithelial BMs in vivo are poorly understood. Myosin-X (MYO10) is a filopodia-inducing protein associated with metastasis and poor clinical outcome in invasive breast cancer (IBC). We identify elevated MYO10 expression in human DCIS and IBC, and this suggests links with disease progression. MYO10 promotes filopodia formation and cell invasion in vitro and cancer-cell dissemination from progressively invasive human DCIS xenografts. However, MYO10-depleted xenografts are more invasive. These lesions exhibit compromised BMs, poorly defined borders, and increased cancer-cell dispersal and EMT-marker-positive cells. In addition, cancer spheroids are dependent on MYO10-filopodia to generate a near-continuous extracellular matrix boundary. Thus, MYO10 is protective in early-stage breast cancer, correlating with tumor-limiting BMs, and pro-invasive at later stages, facilitating cancer-cell dissemination. [Display omitted] • MYO10 expression is elevated at the ductal carcinoma in situ (DCIS) breast cancer stage • MYO10 expression correlates with basement membrane (BM) assembly in DCIS-like xenografts • Loss of MYO10-dependent filopodia impairs BM and induces an EMT-like phenotype in vivo • MYO10 filopodia positively correlate with fibronectin assembly in vitro and in vivo Peuhu, Jacquemet, et al. investigate the role of myosin-X filopodia during breast cancer progression. They report that myosin-X filopodia are protective at the early stage of the disease, contributing to basement membrane integrity, but are pro-invasive at later stages, facilitating cancer-cell dissemination. [ABSTRACT FROM AUTHOR]