Vitamin D deficiency aggravates growth and metastasis of prostate cancer through promoting EMT in two β-catenin-related mechanisms.

Abstract

Increasing evidence has demonstrated that vitamin D deficiency is associated with prostate cancer progression, but its mechanism remains unclear. This study investigated effects of vitamin D deficiency on growth and metastasis of prostate cancer. Nude mice and Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed with vitamin D-deficient (VDD) diets. Prostate cancer growth was aggravated in VDD diet-fed nude mice and TRAMP mice. Invasion and metastasis of prostate cancer were exacerbated in VDD diet-fed TRAMP mice. In vitro experiments showed that calcitriol, an active vitamin D3, inhibited migration and invasion in transforming growth factor (TGF)-β1 -stimulated and -unstimulated PC-3 and DU145 cells. Mechanistically, calcitriol inhibited epithelial-mesenchymal transition (EMT) in TGF-β1 -stimulated and -unstimulated DU145 cells. Unexpectedly, calcitriol did not inhibit Smad2/3 phosphorylation in TGF-β1-stimulated DU145 cells. Instead, calcitriol downregulated expression of proliferation-, metastasis- and EMT-related genes, includes Cyclin D1, MMP7, and Zeb1, by inhibiting interaction between TCF4 and β-catenin. In addition, calcitriol promoted interaction between cytoplasmic VDR and β-catenin, reduced β-catenin phosphorylation and elevated β-catenin/E-cadherin adherens junction complex formation. We provide novel evidence that vitamin D deficiency aggravates growth and metastasis of prostate cancer possibly through promoting EMT in two β-catenin-related mechanisms.

• Authors: Zhi-Hui Zhang, Ming-Dong Liu, Kai Yao, Shen Xu, De-Xin Yu, Dong-Dong Xie, De-Xiang Xu
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 111 Pg. 109177 (01 2023) ISSN: 1873-4847 [Electronic] United States
• PMID: 36223833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022. Published by Elsevier Inc.

Chemical References

• beta Catenin
• Calcitriol
• Transforming Growth Factor beta1

Topics

• Animals
• Male
• Mice
• beta Catenin (metabolism)
• Calcitriol (pharmacology)
• Cell Movement
• Epithelial-Mesenchymal Transition
• Mice, Nude
• Prostatic Neoplasms (pathology)
• Transforming Growth Factor beta1 (metabolism)
• Vitamin D Deficiency