Department of Head and Neck Surgery, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, #145 Shandongzhong Road, Huangpu District, Shanghai, 200001, China.
Mol Cell Biochem. 2017 Nov;435(1-2):87-95. doi: 10.1007/s11010-017-3059-0. Epub 2017 May 27.
The sclerostin domain containing protein 1 (SOSTDC1) is a cell signaling regulator involved in cell physiology and pathology. SOSTDC1 is known to have a suppressive effect on certain kinds of cancer. However, the role of SOSTDC1 in follicular thyroid cancer (FTC) remains unknown. We aimed to investigate if the expression of SOSTDC1 plays any roles in carcinogenesis and metastasis of FTC. We found a significantly down-regulated SOSTDC1 expression in follicular thyroid cancer samples. In addition, our data showed that ectopic expression of SOSTDC1 dramatically inhibited thyroid cancer cell proliferation in vitro and in nude mice. SOSTDC1 also compromised the migratory, invasive property, and epithelial-mesenchymal transition (EMT) activity of FTC cell. Mechanically, SOSTDC1 exerted its tumor suppressor function by inhibiting the activity of major signaling pathways including the phosphatidylinositol-3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/Erk pathways. Altogether, our findings provide insight into the role of SOSTDC1 as a novel functional tumor suppressor in follicular thyroid cancer through modulating the activities of PI3K/Akt and MAPK/Erk signaling pathways.
骨硬化蛋白结构域包含蛋白 1（SOSTDC1）是一种参与细胞生理和病理的细胞信号调节剂。已知 SOSTDC1 对某些癌症具有抑制作用。然而，SOSTDC1 在滤泡状甲状腺癌（FTC）中的作用尚不清楚。我们旨在研究 SOSTDC1 的表达是否在 FTC 的发生和转移中发挥作用。我们发现滤泡状甲状腺癌细胞样本中 SOSTDC1 的表达明显下调。此外，我们的数据表明，SOSTDC1 的异位表达可显著抑制体外和裸鼠中的甲状腺癌细胞增殖。SOSTDC1 还损害了 FTC 细胞的迁移、侵袭特性和上皮-间充质转化（EMT）活性。在机制上，SOSTDC1 通过抑制包括磷脂酰肌醇-3-激酶（PI3K）/Akt 和丝裂原激活蛋白激酶（MAPK）/Erk 途径在内的主要信号通路的活性发挥其肿瘤抑制功能。总之，我们的研究结果为 SOSTDC1 作为通过调节 PI3K/Akt 和 MAPK/Erk 信号通路的活性在滤泡状甲状腺癌中发挥新型功能性肿瘤抑制因子的作用提供了深入了解。
