Christopher A. McCulloch

Colorectal cancer (CRC) is a high prevalence adenocarcinoma with progressive increases in metastasis‐related mortality, but the mechanisms governing the extracellular matrix (ECM) degradation important for metastasis in CRC are not well‐defined. We investigated a functional relationship between vimentin (Vim) and myosin 10 (Myo10), and whether this relationship is associated with cancer progression. We tested the hypothesis that Vim regulates the aggregation of Myo10 at the tips of cell extensions, which increases membrane‐type 1 matrix metalloproteinase (MT1‐MMP)‐associated local collagen proteolysis and ECM degradation. Analysis of CRC samples revealed colocalization of Vim with Myo10 and MT1‐MMP in cell extensions adjacent to sites of collagen degradation, suggesting an association with local cell invasion. We analyzed cultured CRC cells and fibroblasts and found that Vim accelerates aggregation of Myo10 at cell tips, which increases the cell extension rate. Vim stabilizes the interaction of Myo10 with MT1‐MMP, which in turn increases collagenolysis. Vim depletion reduced the aggregation of Myo10 at the cell extension tips and MT1‐MMP‐dependent collagenolysis. We propose that Vim interacts with Myo10, which in turn associates with MT1‐MMP to facilitate the transport of these molecules to the termini of cell extensions and there enhance cancer invasion of soft connective tissues.