N-cadherin promotes thyroid tumorigenesis through modulating major signaling pathways.

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.