Mol Endocrinol 2011 Nov;25 (11): 1858-66. [IF:4.889]
Sphingosine kinase 1 is overexpressed and promotes proliferation in human thyroid cancer.
Guan H , Liu L , Cai J , Liu J , Ye C , Li M , Li Y .
Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou 510080, China. easd04lyb@126.com.
中山大学第一附属医院内分泌及糖尿病中心
Abstract
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.
摘要：
鞘氨醇激酶-1，一种致癌蛋白激酶，之前已被证实能提高多种人体肿瘤的发生率，而且其在肿瘤的发展和进化过程中起着举足轻重的作用。但是，学者们对其在甲状腺肿瘤的发生过程中的生物学及临床特质却知之甚少。现在，我们证实了鞘氨醇激酶-1 的表达引起甲状腺癌的发生增多，而且，其表达水平与甲状腺肿瘤的恶性程度相关。通过对特定的RNA沉默SphK1能减缓甲状腺肿瘤细胞的增殖， SphK1表达水平还与甲状腺癌组织增殖细胞的核抗体表达密切相关。值得注意的是，SphK1的消耗会导致蛋白激酶B、糖原合酶激酶-3β去磷酸化随之导致β-连环蛋白-T-细胞因子/淋巴增强因子失去转录活性。因此，总的来说，我们的研究证实了SphK1是一个活跃的致癌蛋白激酶、Akt/糖原合酶激酶-3β/β-连环蛋白活化剂，也许还是甲状腺癌的生物标记物。
