title: Adiponectin supports cell survival in glucose deprivation through enhancement of autophagic response in colorectal cancer cells.
abstract: 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.
authors.affiliation: Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan. bakershalal@gmail.com
authors.forename: Baker S
authors.initials: BS
authors.lastname: Habeeb
authors.forename: Joji
authors.initials: J
authors.lastname: Kitayama
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D005947:Glucose / Q000172:deficiency*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology
chemical_list: D052242:Adiponectin; D005947:Glucose