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Cancer Sci. 2012 Dec;103(12):2064-71. doi: 10.1111/cas.12019. Epub 2012 Oct 22.

Nuclear receptor coactivator RAC3 inhibits autophagy.

Author information

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

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.

PMID:
22957814
DOI:
10.1111/cas.12019
[Indexed for MEDLINE]
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