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To metastasize and disseminate, carcinoma cells must invade the surrounding extracellular matrix (ECM) and migrate to reach blood or lymphatic vessels. Collagen (CN) and fibronectin (FN), two components of the ECM surrounding tumors, are highly expressed in metastatic tumors and their patterns of expression can correlate with metastatic outcome in patient samples. Mena, an actin regulatory protein, is upregulated in breast cancer and is alternatively spliced to produce protein isoforms with distinct functions during tumor progression. The invasion-specific MenaINV isoform increases metastasis by potentiating tumor cell motility and invasion responses to various growth factors. All Mena isoforms bind directly to the α5 subunit of the α5β1 integrin, an FN receptor. We hypothesized that the interaction between MenaINV and α5β1 plays an important role in integrating signals from the ECM as well as growth factors …