Sphingosine Kinase 1 Is Overexpressed and Promotes Proliferation in Human Thyroid Cancer
Sphingosine Kinase 1 Is Overexpressed and Promotes Proliferation in Human Thyroid Cancer
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鞘氨醇激酶 1 过度表达并促进人类甲状腺癌增殖
DOI：
10.1210/me.2011-1048
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发表时间：
2011-11-01
影响因子：
--
通讯作者：
Li, Yanbing
中科院分区：
文献类型：
--
作者：
Guan, Hongyu;Liu, Liehua;Li, Yanbing
鞘氨酸激酶1 （SphK1）是一种致癌激酶，先前已发现在各种类型的人类癌症中升高，并在肿瘤的发生和进展中发挥作用。然而，SphK1在甲状腺癌中的生物学和临床意义在很大程度上是未知的。本研究表明，SphK1在甲状腺癌中普遍表达上调，其表达水平与甲状腺恶性程度相关。通过特异性RNA干扰沉默SphK1能够抑制甲状腺癌细胞的增殖，并且SphK1的表达水平与甲状腺癌组织中增殖细胞核抗原的表达密切相关。特别值得注意的是，SphK1的缺失导致蛋白激酶B和糖原合成酶激酶3 β的去磷酸化，以及随后β -连环蛋白- t细胞因子/淋巴细胞增强因子转录活性的失活。综上所述，我们的研究已经确定SphK1是一种促增殖的致癌激酶，Akt/糖原合成酶激酶3 β / β -连环蛋白激活剂，也可能是甲状腺癌的生物标志物。（Molecular Endocrinology 25: 1858-1866, 2011）
Sphingosine kinase 1 (SphK1), an oncogenic kinase, has been previously found to be elevated in various types of human cancer and play a role in tumor development and progression. Nevertheless, the biological and clinical significance of SphK1 in thyroid cancer is largely unknown. Here, we demonstrate that the expression of SphK1 is generally up-regulated in thyroid cancer and that its expression level is correlated with the degree of thyroid malignancy. Silencing SphK1 by specific RNA interference is able to suppress the proliferation of thyroid cancer cells, and SphK1 expression level is strongly associated with the expression of proliferation cell nuclear antigen in thyroid cancer tissues. Of particular note is that depletion of SphK1 results in dephosphorylation of protein kinase B and glycogen synthase kinase-3 beta and subsequent inactivation of beta-catenin-T-cell factor/lymphoid enhancing factor transcriptional activity. Hence, taken together, our study has identified SphK1 as a proproliferative oncogenic kinase, an Akt/glycogen synthase kinase-3 beta/beta-catenin activator, and probably a biomarker for thyroid cancer as well. (Molecular Endocrinology 25: 1858-1866, 2011)