Da Chenxing, Wu Kexia, Yue Chenli, Bai Peisong, Wang Rong, Wang Guanjie, Zhao Man, Lv Yanyan, Hou Peng
Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.
Department of Endocrinology, Shanxi Provincial Crops Hospital of Chinese People's Armed Police Force, Xi'an 710054, P.R. China.
Oncotarget. 2017 Jan 31;8(5):8131-8142. doi: 10.18632/oncotarget.14101.
Epithelial-mesenchymal transition (EMT), a crucial step in disease progression, plays a key role in tumor metastasis. N-cadherin, a well-known EMT marker, acts as a major oncogene in diverse cancers, whereas its functions in thyroid cancer remains largely unclear. This study was designed to explore the biological roles and related molecular mechanism of N-cadherin in thyroid tumorigenesis. Quantitative RT-PCR (qRT-PCR) and immunohistochemistry assays were used to evaluate N-cadherin expression. A series of in vitro studies such as cell proliferation, colony formation, cell cycle, apoptosis, migration and invasion assays were performed to determine the effect of N-cadherin on malignant behavior of thyroid cancer cells. Our results showed that N-cadherin was significantly upregulated in papillary thyroid cancers (PTCs) as compared with non-cancerous thyroid tissues. N-cadherin knockdown markedly inhibited cell proliferation, colony formation, cell migration and invasion, and induced cell cycle arrest and apoptosis. On the other hand, ectopic expression of N-cadherin promoted thyroid cancer cell growth and invasiveness. Mechanically, our data demonstrated that tumor-promoting role of N-cadherin in thyroid cancer was closely related to the activities of the MAPK/Erk, the phosphatidylinositol-3-kinase (PI3K)/Akt and p16/Rb signaling pathways in addition to affecting the EMT process. Altogether, our findings suggest that N-cadherin promotes thyroid tumorigenesis by modulating the activities of major signaling pathways and EMT process, and may represent a potential therapeutic target for this cancer.
上皮-间质转化（EMT）是疾病进展中的关键步骤，在肿瘤转移中起关键作用。N-钙黏蛋白是一种著名的EMT标志物，在多种癌症中作为主要癌基因发挥作用，而其在甲状腺癌中的功能仍 largely不清楚。本研究旨在探讨N-钙黏蛋白在甲状腺肿瘤发生中的生物学作用及相关分子机制。采用定量逆转录-聚合酶链反应（qRT-PCR）和免疫组织化学分析来评估N-钙黏蛋白的表达。进行了一系列体外研究，如细胞增殖、集落形成、细胞周期、凋亡、迁移和侵袭分析，以确定N-钙黏蛋白对甲状腺癌细胞恶性行为的影响。我们的结果表明，与非癌性甲状腺组织相比，N-钙黏蛋白在甲状腺乳头状癌（PTC）中显著上调。敲低N-钙黏蛋白明显抑制细胞增殖、集落形成、细胞迁移和侵袭，并诱导细胞周期停滞和凋亡。另一方面，N-钙黏蛋白的异位表达促进甲状腺癌细胞生长和侵袭性。从机制上讲，我们的数据表明，N-钙黏蛋白在甲状腺癌中的促肿瘤作用除了影响EMT过程外，还与丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/Erk）、磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B（Akt）和p16/视网膜母细胞瘤（Rb）信号通路的活性密切相关。总之，我们的研究结果表明，N-钙黏蛋白通过调节主要信号通路的活性和EMT过程促进甲状腺肿瘤发生，可能是这种癌症的潜在治疗靶点。
