Vitamin D receptor regulates proliferation and differentiation of thyroid carcinoma via the E-cadherin-β-catenin complex

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 on 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.

The pyroptosis-related gene signature predicts prognosis and reveals characterization of the tumor immune microenvironment in acute myeloid leukemia

“…Consistently, our study demonstrated that the expression of ELANE was significantly higher while the neutrophil infiltration score was remarkably lower in the low-risk group than that in the high-risk group, which was very likely to be ascribed to its pyroptosis activating effect in neutrophils. In addition, the following three genes ( GSMDA , PYCARD , and VDR ) that were previously identified as possible executors of pyroptosis and usually exhibited tumor-suppressive effects ( Ding et al, 2016 ; Šutić et al, 2019 ; Ling et al, 2022 ) were also identified and included in the present PRG signature, further confirming its reliability.…”

Vitamin D-Related Genes and Thyroid Cancer—A Systematic Review

“…Vitamin D may directly affect the thyroid gland, as thyrocytes express VDR . Numerous studies have shown that the VDR level is increased in the case of DTC (mainly PTC was assessed) in comparison to the normal thyroid [ 18 , 42 , 43 , 44 , 45 , 46 ]. Moreover, VDR was observed among genes overexpressed in the follicular variant of PTC comparing to follicular adenoma [ 47 ].…”

Healthy Lifestyle and Cancer Risk: Modifiable Risk Factors to Prevent Cancer

“…A factor that could suggest a decisive function of vitamin D in the development and advancement of cancer is the presence of the specific receptor for vitamin D on malignant cells and not only on bone cells or cells responsible for calcium regulation [ 81 , 82 ]. There are numerous mechanisms through which vitamin D carries out its anti-tumor actions.…”