title: Reduced expression of AMPK-β1 during tumor progression enhances the oncogenic capacity of advanced ovarian cancer.
abstract: AMP-activated protein kinase (AMPK) is a key energy sensor that is involved in regulating cell metabolism. Our previous study revealed that the subunits of the heterotimeric AMPK enzyme are diversely expressed during ovarian cancer progression. However, the impact of the variable expression of these AMPK subunits in ovarian cancer oncogenesis remains obscure. Here, we provide evidence to show that reduced expression of the AMPK-β1 subunit during tumor progression is associated with the increased oncogenic capacity of advanced ovarian cancer cells. Immunohistochemical analysis revealed that AMPK-β1 levels were reduced in advanced-stage (P = 0.008), high-grade (P = 0.013) and metastatic ovarian cancers (P = 0.008). Intriguingly, down-regulation of AMPK-β1 was progressively reduced from tumor stages 1 to 3 of ovarian cancer. Functionally, enforced expression of AMPK-β1 inhibited ovarian-cancer-cell proliferation, anchorage-independent cell growth, cell migration and invasion. Conversely, depletion of AMPK-β1 by siRNA enhanced the oncogenic capacities of ovarian cancer cells, suggesting that the loss of AMPK-β1 favors the aggressiveness of ovarian cancer. Mechanistically, enforced expression of AMPK-β1 increased AMPK activity, which, in turn, induced cell-cycle arrest via inhibition of AKT/ERK signaling activity as well as impaired cell migration/invasion through the suppression of JNK signaling in ovarian cancer cells. Taken together, these findings suggest that the reduced expression of AMPK-β1 confers lower AMPK activity, which enhances the oncogenic capacity of advanced-stage ovarian cancer.
authors.forename: Cuilan
authors.initials: C
authors.lastname: Li
authors.forename: Vincent W S
authors.initials: VW
authors.lastname: Liu
authors.forename: Pui Man
authors.initials: PM
authors.lastname: Chiu
authors.forename: Kwok-Ming
authors.initials: KM
authors.lastname: Yao
authors.affiliation: Department of Obstetrics & Gynecology, The University of Hong Kong, 6th Floor, Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong, SAR, People's Republic of China. hysngan@hku.hk.
authors.forename: Hextan Y S
authors.initials: HY
authors.lastname: Ngan
authors.forename: David W
authors.initials: DW
authors.lastname: Chan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D018450:Disease Progression; D004789:Enzyme Activation; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology*; D046888:Tissue Array Analysis; D014162:Transfection
chemical_list: D055372:AMP-Activated Protein Kinases