Investigation of a possible functional pathway involving microRNAs, MITF, myosin-Va and adhesion molecules with a role in the metastatic cascade of melanoma

Abstract

Tumor progression and metastasis are complex processes, which involve several changes in the tumor cells and microenvironment. Increase of migratory capacity and resistance of death are the first characteristics observed. Several evidences suggest a possible role to myosin Va in tumor progression and apoptosis. Data from our laboratory indicate that myosin-Va is upregulated in metastatic melanoma cells and knockdown of myosin-Va leads to high rates of anoikis, low capacity to adhere onto fibronectin-coated surface, higher capacity of migration and invasion. Performing a key role in the establishment and progression of tumor are miRNAs, which are located in chromosomal regions susceptible to amplification, deletion or translocations and are able to regulate complex pathways of tumor development. In silico analysis indicate that MYO5A mRNA is target of several miRNA among which, with high score, miR-145, a tumor suppressor miRNA whose loss is correlated with upregulation of the MITF, an oncogenic transcription factor that we showed to function as transcription activator for MYO5A gene in melanocytes. Thus, this project aims to clarify the involvement of myosin Va in invasion and metastasis in vivo and determine its association with both essential adhesives molecules and miRNAs regulatory cascades. Changes in the activity of a functional route involving myosin-Va could influence the behavior of the melanocytes and cause greater propensities to metastasis. (AU)