Role of caveoline-1 in regulating the synthase activity of nitric oxide in Melanoma

Abstract

The increase in melanoma has been increasing in recent years due to increased life expectancy and greater exposure to ultraviolet rays. Melanoma is an extremely aggressive cancer that has a high rate of metastasis and, consequently, high mortality. Late diagnosis, lack of tumor markers, and inefficiency of available therapies are the main factors associated with high lethality. One of the factors that contribute to melanomagenesis is the accumulation of reactive oxygen species (ROS), which leads to an imbalance in redox signaling and activation of oncogenic pathways. One of the sources of ROS in melanoma is a nitric oxide synthase (NOS), a qualification for the production of nitric oxide when there is a reduction in the bioavailability of tetrahydrobiopterin (BH4), the enzyme's cofactor, a process called decoupling. NOS activity in endothelial cells is regulated by integrated components, including the bioavailability of the BH4 cofactor and interaction with caveolin-1, reflected in supramolecular structures of the plasma membrane called caveolae. Caveolin-1 expression is altered without melanoma, contributing positively or negatively in different stages of tumor progression, which seems to be related to differential interaction with other proteins. However, it was not included whether NOS activity could be regulated by caveolin-1 in melanoma. Therefore, the aim of this work is to evaluate the role of caveolin-1 in regulating NOS activity in melanoma.(AU)