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The role of cellular adhesion changes in the regulation of AKT/PKB nuclear localization in melanoma cell lines harboring distinct oncogenic mutations

Grant number: 12/15300-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2012
Effective date (End): August 31, 2013
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Joel Machado Junior
Grantee:Sarah Franco Figueira
Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

The ability to avoid detachment-induced apoptosis (anoikis) is a characteristic of malignant cells with increased tumorigenic and metastatic potentials. Considering that resistance to anoikis is a hallmark of metastatic cancer, it is critical to understand mechanisms governing this process. The signaling cascades underlying anoikis-resistance is not fully understood and it seems to result from an orchestrated array of distinct pathways and extensive cross-talk, which may be regulated in a highly tumor cell-type specific fashion. The serine/threonine kinase AKT/PKB is well known as an important mediator of many cell survival signaling pathways and its role as a central mediator of melanoma survival has been shown in several models of melanoma. Recently, we found phosphorylated AKT into the nucleus of melanoma cells following detachment, suggesting that nuclear translocation of AKT is favored after loss of cell adhesion. Although it has been demonstrated that AKT can undergoes nuclear translocation, the biological outcome of nuclear AKT during tumor progression and metastasis has not been explored. Therefore, the focus of this project is to characterize the presence of AKT into the nucleus of human melanoma cells harboring distinct oncogenic mutations that are frequent in melanoma, as well as to determine if AKT subccellular localization is modulated in consequence of changes in cell adhesion state Characterizing the nucleus as functional target of AKT/PKB may contribute to understand how cellular adhesion changes can affect AKT/PKB cellular localization and function and might also contribute with insights towards establishing new therapeutic strategies based on interfering with AKT/PKB function through regulation of its cellular localization.