MYO10-filopodia support basement membranes at pre-invasive tumor boundaries

The transition from benign ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC) involves the escape of cells through a breach of the basement membrane (BM) that surrounds the DCIS. There has been significant progress in understanding how cancer cells penetrate through BMs, but less is known about how cancer cell progression itself impacts the BM. A recent study by the Ivaska lab identified that Myosin-X (MYO10), an inducer of filipodia, has a profound effect on BM formation around DCIS, and may play opposing roles in early vs late breast cancer progression. Preliminary studies from human patient samples showed elevated levels of MYO10 in DCIS and IBS relative to normal mammary epithelium. These findings were complemented by in vitro studies showing MYO10 promoted filopodia formation, cancer cell invasion, and cancer cell dissemination. Interestingly, knockdown of MYO10 reduced BM formation around DCIS and led to more aggressive dispersal of tumor cells. In vitro experiments with 3D spheroids comprised of control and shMYO10 cells in combination with exogenous, fluorescently labeled fibronectin showed that MYO10-filopodia was important for proper tethering of fibronectin. Collectively, these findings show that in pre-invasive DCIS MYO10 is critical for the formation of proper BM integrity, but as breast cancer progresses the MYO10 will contribute to enhanced invasiveness and tumor progression. Cytoskeleton Inc’s fluorescently labeled ECM proteins, fibronectin (Cat. #FNR02) and laminin (Cat. #LMN02), were essential to defining how MYO10 affected BM formation in vitro.