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

• Grant number: 12/13900-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2012
• End date: August 31, 2015
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Enilza Maria Espreafico
• Grantee: Carmen Lucia Salla Pontes
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ALVES, CLEIDSON P.; YOKOYAMA, SATORU; GOEDERT, LUCAS; PONTES, CARMEN L. S.; SOUSA, JOSANE F.; FISHER, DAVID E.; ESPREAFICO, ENILZA M.. MYO5A Gene Is a Target of MITF in Melanocytes. JOURNAL OF INVESTIGATIVE DERMATOLOGY, v. 137, n. 4, p. 985-989, APR 2017. (12/13900-7, 14/07726-0, 14/18189-5)