βKlotho suppresses tumor growth in hepatocellular carcinoma by regulating Akt/GSK-3β/cyclin D1 signaling pathway.
βKlotho suppresses tumor growth in hepatocellular carcinoma by regulating Akt/GSK-3β/cyclin D1 signaling pathway.
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DOI：
10.1371/journal.pone.0055615
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Ye X;Guo Y;Zhang Q;Chen W;Hua X;Liu W;Yang Y;Chen G
βKlotho是多种代谢过程的调节剂，但其在癌症中的作用仍不清楚。我们发现βKlotho在人肝癌组织中的表达较癌旁肝组织中的表达下调。与正常肝细胞相比，肝癌细胞也显示βKlotho表达降低。将βKlotho重新引入肝癌细胞中抑制其增殖。βKlotho的抗增殖作用可能与Akt/GSK-3β/cyclin D1信号通路介导的G1至S期阻滞有关，因为强制表达βKlotho可降低Akt和GSK-3β的磷酸化水平，并诱导cyclin D1的下调。此外，βKlotho过表达可抑制肿瘤发生，而组成性激活的Akt可在体内推翻βKlotho的抑制作用。这些数据表明βKlotho抑制肝细胞癌的肿瘤生长。
βKlotho is a regulator in multiple metabolic processes, while its role in cancer remains unclear. We found the expression of βKlotho was down-regulated in human hepatocellular carcinoma tissues compared with that in paired adjacent non-tumourous liver tissues. Hepatoma cells also showed decreased expression of βKlotho compared with normal hepatocyte cells. Reintroduction of βKlotho into hepatoma cells inhibited their proliferation. The anti-proliferative effect of βKlotho might be linked with G1 to S phase arrest, which was mediated by Akt/GSK-3β/cyclin D1 signaling, since forced expression βKlotho reduced the phosphorylation level of Akt and GSK-3β and induced down-regulation of cyclin D1. Furthermore, βKlotho overexpression could inhibit tumorgenesis, while constitutively activated Akt could override the suppressive effects of βKlotho in vivo. These data suggest βKlotho suppresses tumor growth in hepatocellular carcinoma.
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