Abstract
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.
Highlights
Thyroid cancer is the most common endocrine malignancy and is one of the most rapidly increasing human cancers worldwide [1]
To explore the role of N-cadherin in thyroid cancer, we first evaluated its mRNA expression in 17 pairs of conventional papillary thyroid cancers (CPTCs) and matched non-cancerous thyroid tissues by quantitative RT-PCR
We found that the expression of N-cadherin protein was markedly upregulated in CPTCs as compared to matched non-cancerous thyroid tissues (Figure 1B)
Summary
Thyroid cancer is the most common endocrine malignancy and is one of the most rapidly increasing human cancers worldwide [1]. The patients with DTC have good prognosis with the low mortality rate, there is a high recurrence rate and potential risk of differentiating into more aggressive and lethal thyroid cancer such as PDTC or ATC [3, 4]. The development of cancer metastasis involves multiple steps. Epithelial-mesenchymal transition (EMT) is considered as an initial and necessary step by which epithelial cells lost their cell polarity and cell-cell adhesion, and gain migratory and invasive properties [6, 7]. A growing body of evidence has shown that several transcription factors are aberrantly expressed in different types of cancer, contributing to the precess of EMT through negatively regulating E-cadherin transcription, including Snail, Twist and Slug [7, 11]. The exact functions of N-cadherin in thyroid tumorigenesis remains largely unknown
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