• Open Access

Nuclear receptor coactivator RAC3 inhibits autophagy

Authors

  • Pablo Nicolas Fernandez Larrosa,

    1. Laboratory of Molecular Biology and Apoptosis, (IDIM-CONICET), University of Buenos Aires, Buenos Aires, Argentina
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    • These authors contributed equally to this work.
  • Cecilia Viviana Alvarado,

    1. Laboratory of Molecular Biology and Apoptosis, (IDIM-CONICET), University of Buenos Aires, Buenos Aires, Argentina
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    • These authors contributed equally to this work.
  • Maria Fernanda Rubio,

    1. Laboratory of Molecular Biology and Apoptosis, (IDIM-CONICET), University of Buenos Aires, Buenos Aires, Argentina
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    • Member of the Argentine National Research Council (CONICET).
  • Marina Ruiz Grecco,

    1. Laboratory of Molecular Biology and Apoptosis, (IDIM-CONICET), University of Buenos Aires, Buenos Aires, Argentina
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  • Sabrina Micenmacher,

    1. Laboratory of Molecular Biology and Apoptosis, (IDIM-CONICET), University of Buenos Aires, Buenos Aires, Argentina
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  • Giselle Astrid Martinez-Noel,

    1. Laboratory of Molecular Biology and Apoptosis, (IDIM-CONICET), University of Buenos Aires, Buenos Aires, Argentina
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    • Member of the Argentine National Research Council (CONICET).
  • Laura Panelo,

    1. Laboratory of Molecular Biology and Apoptosis, (IDIM-CONICET), University of Buenos Aires, Buenos Aires, Argentina
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  • Monica Alejandra Costas

    Corresponding author
    • Laboratory of Molecular Biology and Apoptosis, (IDIM-CONICET), University of Buenos Aires, Buenos Aires, Argentina
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    • These authors contributed equally to this work.
    • Member of the Argentine National Research Council (CONICET).

To whom correspondence should be addressed.

E-mail: costas.monica@lanari.fmed.uba.ar

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.

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