Unconventional myosin VIIA promotes melanoma progression

Abstract

Unconventional myosin VIIA (Myo7a) is an actin-based motor molecule that normally functions in cochlear hair cells of the inner ear. Mutations of MYO7A/Myo7a have been implicated in inherited deafness in both humans and mice. However, there is limited information about the functions of Myo7a outside of the specialized cells of the ears. Herein, we report a previously-unidentified function of Myo7a by demonstrating that it plays an important role in melanoma progression. We found that silencing Myo7a by RNAi inhibited melanoma cell growth by upregulation of cell cycle regulator p21 and suppressed melanoma cell migration and invasion by downregulation of RhoGDI2 and MMP9. Further, Myo7a depletion suppressed melanoma cell metastases to the lung, kidney, and bone in mice. In contrast, overexpression of Myo7a promoted melanoma xenograft growth and lung metastasis. Importantly, Myo7a levels are remarkably elevated in human melanoma patients. Collectively, we demonstrated for the first time that Myo7a is able to function in non-specialized cells, a finding that reveals the complicated disease-related roles of Myo7a, especially in melanomas.