Adiponectin antagonizes the oncogenic actions of leptin in hepatocellular carcinogenesis.
Adiponectin antagonizes the oncogenic actions of leptin in hepatocellular carcinogenesis.
复制标题
DOI：
10.1002/hep.23892
复制
发表时间：
2010-11
期刊：
影响因子：
13.5
通讯作者：
Saxena, Neeraj K.
中科院分区：
文献类型：
--
作者：
Sharma, Dipali;Wang, Jason;Fu, Ping P.;Sharma, Shvetank;Nagalingam, Arumugam;Mells, Jamie;Handy, Jeffrey;Page, Andrew J.;Cohen, Cynthia;Anania, Frank A.;Saxena, Neeraj K.
Obesity is rapidly becoming a pandemic and is associated with increased carcinogenesis. Obese populations have higher circulating levels of leptin in contrast to low concentrations of adiponectin. Hence, it is important to evaluate the dynamic role between adiponectin and leptin in obesity-related carcinogenesis. Recently, we reported the oncogenic role of leptin including its potential to increase tumor invasiveness and migration of hepatocellular carcinoma (HCC) cells. In the present study, we investigated whether adiponectin could antagonize the oncogenic actions of leptin in HCC. We employed HCC cell-lines HepG2 and Huh7, nude mice-xenograft model of HCC and immunohistochemistry-data from tissue-microarray to demonstrate the antagonistic role of adiponectin on the oncogenic actions of leptin. Adiponectin treatment inhibited leptin-induced cell proliferation of HCC cells. Using scratch-migration and electric cell-substrate impedance-sensing based migration assays, we found that adiponectin inhibited leptin-induced migration of HCC cells. Adiponectin treatment effectively blocked leptin-induced invasion of HCC cells in matrigel invasion assays. While leptin inhibited apoptosis in HCC cells, we found that adiponectin treatment induced apoptosis even in the presence of leptin. Analysis of the underlying molecular mechanisms revealed that adiponectin treatment reduced leptin-induced Stat3 and Akt phosphorylation. Adiponectin also increased suppressor of cytokine signaling (SOCS3), a physiologic negative regulator of leptin signal transduction. Importantly, adiponectin significantly reduced leptin-induced tumor burden in nude mice. In HCC samples, leptin expression significantly correlated with HCC proliferation as evaluated by Ki-67 while adiponectin expression correlated significantly with increased disease-free-survival and inversely with tumor size and local recurrence. Collectively, these data demonstrate that adiponectin has the molecular potential to inhibit the oncogenic actions of leptin by blocking downstream effector molecules.
登录
查看更多内容
影响因子：
82.9
作者：
Berg, AH;Combs, TP;Scherer, PE
通讯作者：
Scherer, PE
影响因子：
4.8
作者：
Bjorbaek, C;Uotani, S;Flier, JS
通讯作者：
Flier, JS
影响因子：
4.8
作者：
Saxena, Neeraj K.;Vertino, Paula M.;Sharma, Dipali
通讯作者：
Sharma, Dipali
影响因子：
4.8
作者：
Bjorbæk, C;El-Haschimi, K;Flier, JS
通讯作者：
Flier, JS
影响因子：
4.8
作者：
Saxena, NK;Titus, MA;Anania, FA
通讯作者：
Anania, FA