title: Nuclear receptor coactivator RAC3 inhibits autophagy.
abstract: 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.
authors.affiliation: Laboratory of Molecular Biology and Apoptosis, (IDIM-CONICET), University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Pablo Nicolas
authors.initials: PN
authors.lastname: Fernandez Larrosa
authors.forename: Cecilia Viviana
authors.initials: CV
authors.lastname: Alvarado
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Rubio
authors.forename: Marina
authors.initials: M
authors.lastname: Ruiz Grecco
authors.forename: Sabrina
authors.initials: S
authors.lastname: Micenmacher
authors.forename: Giselle Astrid
authors.initials: GA
authors.lastname: Martinez-Noel
authors.forename: Laura
authors.initials: L
authors.lastname: Panelo
authors.forename: Monica Alejandra
authors.initials: MA
authors.lastname: Costas
mesh_terms: D001343:Autophagy; D015687:Cell Hypoxia; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics; D056918:Nuclear Receptor Coactivators / Q000235:genetics / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D056918:Nuclear Receptor Coactivators; C411563:RAC3 protein, human; D020744:rac GTP-Binding Proteins