Open AccessNuclear receptor coactivator RAC3 inhibits autophagy
Author(s) -
Fernandez Larrosa Pablo Nicolas,
Alvarado Cecilia Viviana,
Rubio Maria Fernanda,
Ruiz Grecco Marina,
Micenmacher Sabrina,
MartinezNoel Giselle Astrid,
Panelo Laura,
Costas Monica Alejandra
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12019
Subject(s) - autophagy , coactivator , cancer research , microbiology and biotechnology , oncogene , hypoxia (environmental) , suppressor , cytoplasm , biology , tumor suppressor gene , cell , chemistry , gene , transcription factor , cell cycle , carcinogenesis , apoptosis , genetics , organic chemistry , oxygen
RAC 3 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 RAC 3 overexpression inhibits autophagy when induced by starvation or rapamycin and involves RAC 3 nuclear translocation‐dependent and ‐independent mechanisms. Moreover, hypoxia inhibits the RAC 3 gene expression leading to the autophagy process, allowing tumor cells to survive until angiogenesis occurs. The interplay between RAC 3, hypoxia, and autophagy could be an important mechanism for tumor progression and a good target for a future anticancer therapy.