Functional Analysis of NOX4 Overexpression in the Acquisition of Metastatic Characteristics in Human Melanoma Cells from Primary Site A-375

• Grant number: 24/00085-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2024
• Effective date (End): June 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Hugo Pequeno Monteiro
• Grantee: Laura Morales Peres
• Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/15038-7 - Tumor development under the perspective of redox signaling: temporal modulation of the production of nitric oxide and reactive oxygen species, AP.TEM

Abstract

Cancer represents a threat to the population's quality of life, being one of the main causes of mortality globally. Melanoma, a skin cancer, stands out as a particularly aggressive neoplasm, characterized by its high metastatic capacity and, consequently, unfavorable prognosis for patients. Previous research reveals that reactive oxygen species (ROS) are positive mediators of cellular processes important for tumor progression, such as cell proliferation, migration, invasion, and resistance of cells to the adverse environment. In this scenario, the isoforms of the NADPH oxidases (NOX) enzymes, which produce ROS, emerge as protagonists in these processes. Among these isoforms, NOX4 plays a relevant role and has aroused interest in the context of melanoma. Based on these premises, the present research project aims to investigate whether overexpression of the NOX4 isoform, carried out using CRISPR technology, is capable of inducing the acquisition of metastatic characteristics in cells of the primary human melanoma lineage A-375 . To achieve this purpose, the parental cell lines A-375, A-375 NOX4+ and V0 (empty vector) will be used in experiments to evaluate the morphological variations between the lines, as well as the capacity for migration, invasion and clonogenicity. Studies on this topic are important to deepen knowledge about the roles of ROS in regulating tumor progression and can be used to identify new, more specific therapeutic targets.