Abstract
SummaryWe investigated the myosin expression profile in prostate cancer cell lines and found that Myo1b, Myo9b, Myo10, and Myo18a were expressed at higher levels in cells with high metastatic potential. Moreover, Myo1b and Myo10 were expressed at higher levels in metastatic tumors. Using an siRNA-based approach, we found that knockdown of each myosin resulted in distinct phenotypes. Myo10 knockdown ablated filopodia and decreased 2D migration speed. Myo18a knockdown increased circumferential non-muscle myosin 2A-associated actin filament arrays in the lamella and reduced directional persistence of 2D migration. Myo9b knockdown increased stress fiber formation, decreased 2D migration speed, and increased directional persistence. Conversely, Myo1b knockdown increased numbers of stress fibers but did not affect 2D migration. In all cases, the cell spread area was increased and 3D migration potential was decreased. Therefore, myosins not only act as molecular motors but also directly influence actin organization and cell morphology, which can contribute to the metastatic phenotype.
Highlights
Myosins are a large and diverse family of molecular motors important for cell migration and motility
We investigated the myosin expression profile in prostate cancer cell lines and found that Myo1b, Myo9b, Myo10, and Myo18a were expressed at higher levels in cells with high metastatic potential
Myo18a knockdown increased circumferential non-muscle myosin 2A-associated actin filament arrays in the lamella and reduced directional persistence of 2D migration
Summary
Myosins are a large and diverse family of molecular motors important for cell migration and motility. The human genome encodes 39 myosin genes, subdivided into 12 different classes (Berg et al, 2001; Peckham and Knight, 2009). The remaining three encode the non-muscle (NM) myosin isoforms 2A, 2B, and 2C, which contribute to cell shape, adhesion, and cytokinesis (Mogilner and Keren, 2009; Vicente-Manzanares et al, 2009). Myosin isoforms in the remaining classes contribute to a wide range of functions, including organelle trafficking, membrane tethering, Golgi organization, actin organization, and actin polymerization (Hartman and Spudich, 2012). Individual cell types only express a subset of myosin genes. Some myosin isoforms are expressed widely, whereas others (e.g., Myo7a and Myo3) are restricted to a small tissue subset (Doseand Burnside, 2000; Hasson et al, 1995)
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