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

Abstract

hyroid 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.

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See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- Vitamin D (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

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- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- Neuroblastoma: Complete objective response to biological treatment;

- Oesophageal squamocellular carcinoma: a complete and objective response.