Nuclear receptor coactivator RAC3 inhibits autophagy

• Published in: Cancer science Vol. 103; no. 12; pp. 2064 - 2071
• Main Authors: Fernandez Larrosa, Pablo Nicolas, Alvarado, Cecilia Viviana, Rubio, Maria Fernanda, Ruiz Grecco, Marina, Micenmacher, Sabrina, Martinez‐Noel, Giselle Astrid, Panelo, Laura, Costas, Monica Alejandra
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.12.2012
• Subjects: Autophagy; Cell Hypoxia; Cell Nucleus - metabolism; Cytoplasm - metabolism; Gene Expression; Genes, Tumor Suppressor; HEK293 Cells; Humans; Neoplasms - genetics; NF-kappa B - genetics; NF-kappa B - metabolism; Nuclear Receptor Coactivators - genetics; Nuclear Receptor Coactivators - metabolism; Original; rac GTP-Binding Proteins - genetics; rac GTP-Binding Proteins - metabolism
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12019

RAC3 is an oncogene naturally overexpressed in several tumors. Besides its role as coactivator, it can exert several protumoral cytoplasmic actions. Autophagy was found to act either as a tumor suppressor during the early stages of tumor development, or as a protector of the tumor cell in later stages under hypoxic conditions. We found that RAC3 overexpression inhibits autophagy when induced by starvation or rapamycin and involves RAC3 nuclear translocation‐dependent and ‐independent mechanisms. Moreover, hypoxia inhibits the RAC3 gene expression leading to the autophagy process, allowing tumor cells to survive until angiogenesis occurs. The interplay between RAC3, hypoxia, and autophagy could be an important mechanism for tumor progression and a good target for a future anticancer therapy.