Abstract
Thyroid cancer has the fastest rising incidence among cancers, especially for differentiated thyroid carcinoma (DTC). Although the prognosis of DTC is relatively good, if it changes to anaplastic thyroid carcinoma (ATC), the prognosis will be very poor. The prognosis of DTC is largely depending on the degree of cell differentiation and proliferation. However, whether the vitamin D receptor (VDR) plays a role in regulating the proliferation and the differentiation of DTC cells is unclear. In the present study, we found that VDR was upregulated in DTC tissues compared to the adjacent non-cancerous tissue. Knockdown of VDR increased proliferation and decreased differentiation proliferation in DTC cells in vitro as well as DTC cell-derived xenografts in vivo. In contrast, overexpression of VDR had an opposite effect. Knockdown of E-cadherin abolished VDR-induced suppression of proliferation and enhancement of differentiation of the DTC cells. Knockdown of β-catenin partially reversed the effect of the VDR knockdown. VDR increases the levels of E-cadherin in the plasma membrane and decreases the levels of β-catenin in the nucleus. VDR binds to E-cadherin and β-catenin in the plasma membrane of the DTC cell. Taken together, VDR inhibits DTC cell proliferation and promotes differentiation via regulation of the E-cadherin/β-catenin complex, potentially representing novel clues for a therapeutic strategy to attenuate thyroid cancer progression.
Highlights
Thyroid carcinoma is one of the most common endocrine cancers worldwide and its incidence has been rising in the past decades, becoming one of the tumors with the fastest increase (Lim et al, 2017)
The results showed that vitamin D receptor (VDR) expression was increased significantly in the papillary thyroid carcinoma (PTC) tissue compared with paired adjacent non-cancerous thyroid tissue, and VDR staining was mainly localized in most cytoplasm and plasma membrane of PTC, whereas VDR staining was localized in the nucleus of paired adjacent non-cancerous thyroid tissue (Fig. 1A)
The results showed that the expression of VDR was higher in both K1 and WRO cell lines compared with Nthy-ori-3-1 cells
Summary
Thyroid carcinoma is one of the most common endocrine cancers worldwide and its incidence has been rising in the past decades, becoming one of the tumors with the fastest increase (Lim et al, 2017). It can be divided into papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), anaplastic thyroid carcinoma (ATC), and medullary thyroid carcinoma (MTC). ATC accounts for 1% of all thyroid cancers with a poor survival (Ain, 1998; Fagin and Wells, 2016) For these reasons, it is important to understand the characteristics of the tumor at the early stage and to better prevent the progression of the tumor
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