Guan Hongyu, Liu Liehua, Cai Junchao, Liu Juan, Ye Caisheng, Li Mengfeng, Li Yanbing
Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Mol Endocrinol. 2011 Nov;25(11):1858-66. doi: 10.1210/me.2011-1048. Epub 2011 Sep 22.
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-3β and subsequent inactivation of β-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-3β/β-catenin activator, and probably a biomarker for thyroid cancer as well.
鞘氨醇激酶1（SphK1）是一种致癌激酶，此前已发现在各类人类癌症中其表达水平升高，并在肿瘤发生发展过程中发挥作用。然而，SphK1在甲状腺癌中的生物学及临床意义在很大程度上仍不清楚。在此，我们证明SphK1的表达在甲状腺癌中通常上调，且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和糖原合酶激酶-3β去磷酸化，随后β-连环蛋白-T细胞因子/淋巴细胞增强因子转录活性失活。因此，综合来看，我们的研究已确定SphK1是一种促进增殖的致癌激酶、一种Akt/糖原合酶激酶-3β/β-连环蛋白激活剂，并且可能也是甲状腺癌的一种生物标志物。
