BACKGROUND: Alterations of adiponectin (APN), one of the adipokines, have been associated with human cancers. However, the clinical significance and impacts of APN on hepatocellular carcinoma (HCC) remain undetermined. METHODS: Using immunohistochemistry, expression patterns of APN were semiquantitatively scored and further statistically correlated with clinicopathological characteristics and patient survival. Furthermore, the bioeffects and underlying mechanisms of ectopic APN overexpression were determined in Hep3B and HepG2 cells by XTT, immunoblotting, flowcytometry, and invasion assays with or without chemical inhibitors and neutralization antibody. RESULTS: We found that cytoplasmic APN staining in 85 cancerous lesions was increased and associated with a poor survival rate (P = 0.007), even when using the Cox regression model (OR = 3.590; 95 % CI = 1.240-10.394; P = 0.018). Ectopic overexpression of APN in Hep3B and HepG2 cells increased proliferation and invasion as well as the levels of p-AKT (Ser473), p-STAT3 (Tyr705), and those downstream, i.e., cyclin D1 and β-catenin. Similar results were also demonstrated in a stable APN-overexpressing clone, HepG2#136. APN neutralization antibody and LY294002 blocked the APN-mediated effects via inhibition of activated AKT. CONCLUSIONS: Our results suggest that increased APN may contribute to HCC at least in part through its activation of AKT signalling and may serve as a prognostic factor in HCC.
BACKGROUND: Alterations of adiponectin (APN), one of the adipokines, have been associated with humancancers. However, the clinical significance and impacts of APN on hepatocellular carcinoma (HCC) remain undetermined. METHODS: Using immunohistochemistry, expression patterns of APN were semiquantitatively scored and further statistically correlated with clinicopathological characteristics and patient survival. Furthermore, the bioeffects and underlying mechanisms of ectopic APN overexpression were determined in Hep3B and HepG2 cells by XTT, immunoblotting, flowcytometry, and invasion assays with or without chemical inhibitors and neutralization antibody. RESULTS: We found that cytoplasmic APN staining in 85 cancerous lesions was increased and associated with a poor survival rate (P = 0.007), even when using the Cox regression model (OR = 3.590; 95 % CI = 1.240-10.394; P = 0.018). Ectopic overexpression of APN in Hep3B and HepG2 cells increased proliferation and invasion as well as the levels of p-AKT (Ser473), p-STAT3 (Tyr705), and those downstream, i.e., cyclin D1 and β-catenin. Similar results were also demonstrated in a stable APN-overexpressing clone, HepG2#136. APN neutralization antibody and LY294002 blocked the APN-mediated effects via inhibition of activated AKT. CONCLUSIONS: Our results suggest that increased APN may contribute to HCC at least in part through its activation of AKT signalling and may serve as a prognostic factor in HCC.
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Authors: Xi C He; Tong Yin; Justin C Grindley; Qiang Tian; Toshiro Sato; W Andy Tao; Raminarao Dirisina; Kimberly S Porter-Westpfahl; Mark Hembree; Teri Johnson; Leanne M Wiedemann; Terrence A Barrett; Leroy Hood; Hong Wu; Linheng Li Journal: Nat Genet Date: 2007-01-21 Impact factor: 38.330
Authors: Abby B Siegel; Abhishek Goyal; Marcela Salomao; Shuang Wang; Valerie Lee; Christine Hsu; Rosa Rodriguez; Dawn L Hershman; Robert S Brown; Alfred I Neugut; Jean Emond; Tomoaki Kato; Benjamin Samstein; David Faleck; Raffi Karagozian Journal: Oncology Date: 2014-10-03 Impact factor: 2.935
Authors: Tomi Akinyemiju; Justin Xavier Moore; Suzanne E Judd; Maria Pisu; Michael Goodman; Virginia J Howard; Leann Long; Monika Safford; Susan C Gilchrist; Mary Cushman Journal: Oncotarget Date: 2018-02-23