Open AccessAdiponectin supports cell survival in glucose deprivation through enhancement of autophagic response in colorectal cancer cells
Author(s) -
Habeeb Baker S.,
Kitayama Joji,
Nagawa Hirokazu
Publication year - 2011
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/j.1349-7006.2011.01902.x
Subject(s) - autophagy , pi3k/akt/mtor pathway , protein kinase b , adiponectin , ampk , endocrinology , cell growth , protein kinase a , medicine , biology , cancer research , microbiology and biotechnology , chemistry , phosphorylation , signal transduction , insulin , biochemistry , insulin resistance , apoptosis
Adiponectin is known to have suppressive effects on tumor growth and is thought to be a key molecule in the positive correlation between obesity and cancer. However, the detailed mechanisms regulating tumor cell activity have not been elucidated. In this study, we found that both full‐length (f‐Ad) and globular adiponectin (g‐Ad) inhibited cell growth in colon cancer cell lines in glucose‐containing medium, whereas it supported cell survival in glucose‐deprived medium, with an increase in AdipoR1 and AdipoR2 expression. The latter effect of adiponectin in glucose deprivation was significantly inhibited by adding autophagy inhibitors, chloroquine, 3‐methyl adenine or a combination of pepstatin A and E‐64d, suggesting that the effect of supporting cell growth was dependent, at least in part, on the induction of autophagy. The enhancement of autophagy was confirmed morphologically using green fluorescent protein (GFP)‐microtubule‐associated protein 1 light chain 3 (LC3) fusion proteins under a fluorescence microscope using stably transfected DLD‐1 cells expressing GFP‐LC3. Western blot analysis revealed that adiponectin increased the expression of LC3‐1, LC3‐2, phosphorylated AMPKα and PPARα but decreased that of phosphorylated mTOR, insulin like growth factor (IGF)‐1, phosphorylated serine/threonine kinase (Akt) and phosphorylated phosphatidylinositol 3‐kinase (PI3K) in glucose‐deprived medium. We conclude that adiponectin supports cell survival in glucose deprivation through enhancement of the autophagic machinery by AMPKα and PPARα activation and IGF‐1/PI3k/Akt/mTOR pathway inhibition. The bimodal effects of adiponectin are thought to be clinically important in the pathophysiology of tumor development and progression. ( Cancer Sci 2011; 102: 999–1006)