Role of peri/epicellular disulfide isomerase protein (pecPDI) in cytoskeletal organization and survival of melanoma cells

• Grant number: 18/04819-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2018
• End date: December 31, 2018
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Lucia Rossetti Lopes
• Grantee: Stephany Beyerstedt
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID

Abstract

Focal adhesions are essential for the cellular anchorage to extracellular matrix. Its formation depends on a redox-sensible signaling that involves de regulation of a number of enzymes, such as the activation of the focal adhesion kinase(FAK), by reactive oxygen species (ROS). In melanoma cells the main source of ROS is Nox4, a subtype of the NADPH oxidase. PDI is a thiol oxidase reductase from the thioredoxin family, and can interact with Nox4 and regulate its activity via a redox-sensible mechanism, as seen by our group on vascular smooth muscle and endothelial cells. PDI secreted in the extracellular space or located on the cell membrane is called pecPDI. Recent studies from our group demonstrate that this PDI would play an important role in the regulation of the vascular cytoskeleton and its inhibition would decrease the phosphorylation of FAK. Inhibition of Nox4 results in cytoskeletal modifications and less viability in melanoma cells. The contribution of pecPDI in this effect is unknown. Therefore, based on the importance of Nox4 for the formation of focal adhesions and PDI participation in the activation of NADPH oxidase, this project aims to investigate the role of pecPDI in cytoskeletal regulation and survival of melanoma via Nox4, focusing on the signaling pathway of FAK in the formation of focal adhesions. (AU)