Adiponectin suppresses tumor growth of nasopharyngeal carcinoma through activating AMPK signaling pathway.
Adiponectin suppresses tumor growth of nasopharyngeal carcinoma through activating AMPK signaling pathway.
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脂联素通过激活AMPK信号通路抑制鼻咽癌肿瘤生长
DOI：
10.1186/s12967-022-03283-0
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发表时间：
2022-02-14
影响因子：
7.4
通讯作者：
Li F
中科院分区：
文献类型：
--
作者：
Zhang Z;Du J;Shi H;Wang S;Yan Y;Xu Q;Zhou S;Zhao Z;Mu Y;Qian C;Zhao AZ;Cao S;Li F
脂联素是一种脂肪细胞分泌的细胞因子，可增强胰岛素敏感性，减轻炎症。尽管循环中的脂联素水平通常与多种恶性肿瘤呈负相关，但其在鼻咽癌(NPC)发生发展中的作用尚不清楚。在这里，我们研究了循环脂联素水平与鼻咽癌的临床相关性，并研究了脂联素在体外和体内对鼻咽癌生长的影响及其潜在机制。在两个不同的队列中评估了循环脂联素水平与鼻咽癌发病风险之间的关系，包括以医院为基础的病例对照研究，包括152例病例和132名对照，以及一项嵌套的病例对照研究，其中71例病例和142名对照在基于社区的鼻咽癌筛查队列中。采用肿瘤异种移植模型、细胞增殖和细胞周期分析等方法证实脂联素对鼻咽癌细胞生长和移植瘤生长的影响。我们还用各种特定的药物抑制剂和生化分析研究了潜在的信号转导机制。在以医院为基础的病例对照研究和嵌套病例对照研究中，高脂联素水平与男性鼻咽癌风险单调下降的趋势有关。在体外，重组人全长脂联素明显抑制鼻咽癌细胞的生长，并使细胞周期受阻，这种抑制作用依赖于AMPK信号通路。携带遗传性脂联素缺陷的裸鼠鼻咽癌移植瘤生长明显加快。脂联素受体激动剂AdipoRon在人异种移植模型中显示出很强的抗肿瘤活性。这些发现首次证明循环脂联素不仅与鼻咽癌呈负相关，而且通过AMPK信号通路控制鼻咽癌的发展。刺激脂联素功能可能成为鼻咽癌一种新的治疗方式。网上版载有补充材料，可在10.1186/s12967-022-03283-0查阅。
Adiponectin is an adipocyte-secreted cytokine that enhances insulin sensitivity and attenuates inflammation. Although circulating adiponectin level is often inversely associated with several malignancies, its role in the development of nasopharyngeal carcinoma (NPC) remains unclear. Here, we investigated the clinical association between circulating adiponectin level and NPC, and examined the impact of adiponectin, as well as the underlying mechanisms, on NPC growth both in vitro and in vivo. The association between circulating adiponectin level and the risk of developing NPC was assessed in two different cohorts, including a hospital-based case–control study with 152 cases and 132 controls, and a nested case–control study with 71 cases and 142 controls within a community-based NPC screening cohort. Tumor xenograft model, cell proliferation and cycle assays were applied to confirm the effects of adiponectin on NPC growth in cultured cells and in xenograft models. We also investigated the underlying signaling mechanisms with various specific pharmacological inhibitors and biochemistry analysis. High adiponectin levels were associated with a monotonic decreased trend of NPC risk among males in both the hospital-based case–control study and a nested case–control study. In vitro, recombinant human full-length adiponectin significantly inhibited NPC cell growth and arrested cell cycle, which were dependent on AMPK signaling pathway. The growth of xenograft of NPC tumor was sharply accelerated in the nude mice carrying genetic adiponectin deficiency. An adiponectin receptor agonist, AdipoRon, displayed strong anti-tumor activity in human xenograft models. These findings demonstrated for the first time that circulating adiponectin is not only inversely associated with NPC, but also controls the development of NPC via AMPK signaling pathway. Stimulation of adiponectin function may become a novel therapeutic modality for NPC. The online version contains supplementary material available at 10.1186/s12967-022-03283-0.
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影响因子：
11
作者：
Ng, Roy Chun-Laam;Jian, Min;Chan, Koon-Ho
通讯作者：
Chan, Koon-Ho
影响因子：
37.8
作者：
Okamoto, Y;Kihara, S;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
尿激酶型纤溶酶原激活剂受体信号传导在鼻咽癌细胞生长和转移中至关重要
影响因子：
4.3
作者：
Bao, Ying-Na;Cao, Xue;Qian, Chao-Nan
通讯作者：
Qian, Chao-Nan
影响因子：
5
作者：
Liu, Zhiwei;Ji, Ming-Fang;Cao, Su-Mei
通讯作者：
Cao, Su-Mei
DOI：
10.1152/ajpendo.00110.2003
发表时间：
2003-09-01
影响因子：
5.1
作者：
Bruun, JM;Lihn, AS;Richelsen, B
通讯作者：
Richelsen, B