Stimulation of cell invasion by the Golgi Ion Channel GAAP/TMBIM4 via an H2O2-Dependent Mechanism

• Autor(a) principal: Almeida, Nuno
• Data de Publicação: 2020
• Outros Autores: Carrara, Guia, Palmeira, Carlos M., Fernandes, Ana S., Parsons, Maddy, Smith, Geoffrey L., Saraiva, Nuno
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/106653; https://doi.org/10.1016/j.redox.2019.101361
• topic: Calcium; Cell invasion; Golgi apparatus; Hydrogen peroxide; Metabolism; TMBIM; Animals; Calcium Signaling; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Survival; Humans; Hydrogen Peroxide; MCF-7 Cells; Membrane Proteins; Mice; Mitochondria; Neoplasm Invasiveness; Neoplasm Transplantation; Neoplasms; Reactive Oxygen Species; Up-Regulation

The mechanisms by which the Golgi apparatus (GA) impacts on cell invasion are poorly understood. The human Golgi Anti-Apoptotic Protein (hGAAP, also known as TMBIM4) is a highly conserved Golgi cation channel that modulates intracellular Ca2+ fluxes. Human GAAP is expressed in all human tissues, is essential for cell viability and provides resistance against a range of apoptotic stresses. Furthermore, hGAAP enhances adhesion and cell migration by increasing the turnover of focal adhesions due to activation of store-operated Ca2+ entry. Here, we describe a GA-derived mechanism that controls cell invasion. The overexpression of hGAAP stimulates 3-dimensional proteolytic cell invasion by a mechanism that is dependent on the accumulation of intracellular hydrogen peroxide, which might be produced by the hGAAP-dependent stimulation of mitochondrial respiration. These findings provide new insight into the complex mechanisms by which Ca2+ and reactive oxygen species signaling contribute to cell invasion and to the role of the GA in these processes.