Elucidating the role of cortactin in invadopodium-based ECM degradation

Clarke, Marguerite Jean
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University of Guelph

Cortactin is a key player in the invasion of breast cancer cells due to its involvement in actin polymerization, activation of the Arp2/3 complex, and trafficking of the extracellular matrix degrading protein membrane-type-1 matrix metalloproteinase (MT1-MMP). The goal of this study was to assess how particular residues of cortactin, tryptophan 22 (W22), lysine 309 (K309), and tyrosine 421 (Y421), are important in invadopodia formation and ECM degradation. We used quick-change mutagenesis to produce cortactin with mutations at these sites and transfected them into MDA-MB-231 cells to assess their effects on this already invasive, immortalized breast cancer cell line. We found that each mutant expressed a dominant negative effect on these cells, impeding actin polymerization, limiting the cell’s capacity to degrade gelatin (an ECM analogue), and reducing MT1-MMP cell surface expression. Together, these results indicate that cortactin has extensive protein interactions and has a powerful role in invadopodia function.

MT1-MMP, Cortactin, breast cancer, Arp2/3, actin polymerization, invadopodia