Knocking out the Vitamin D Receptor Enhances Malignancy and Decreases Responsiveness to Vitamin D3 Hydroxyderivatives in Human Melanoma Cells

Cancers

Krystyna Urbanska¹  Ewa Podgorska²  Andrzej T. Slominski²  Tae-Kang Kim²  Zorica Janjetovic²  Sejong Bae³  Robert C. Tuckey⁴ 

[1] Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Kraków, 31-007 Kraków, Poland;Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA;School of Molecular Sciences, University of Western Australia, Perth, WA 6009, Australia;

关键词: melanoma;    vitamin D;    vitamin D receptor;    active forms of vitamin D;    malignancy;   

DOI  :  10.3390/cancers13133111

来源: DOAJ

【 摘 要 】

Vitamin D3 is not only involved in calcium and phosphate metabolism in humans, but it can also affect proliferation and differentiation of normal and cancer cells, including melanoma. The mechanism of the anti-cancer action of vitamin D3 is not fully understood. The nuclear vitamin D receptor (VDR) is crucial for the phenotypic effects of vitamin D hydroxyderivatives. VDR expression shows an inverse correlation with melanoma progression and poor outcome of the disease. In this study we knocked out the VDR in a human melanoma cell line using CRISPR methodology. This enhanced the proliferation of melanoma cells grown in monolayer culture, spheroids or colonies and their migration. Activated forms of vitamin D, including classical 1,25(OH)₂D3, 20(OH)D3 and 1,20(OH)₂D3, inhibited cell proliferation, migration rate and the ability to form colonies and spheroids in the wild-type melanoma cell line, while VDR KO cells showed a degree of resistance to their action. These results indicate that expression of VDR is important for the inhibition of melanoma growth induced by activated forms of vitamin D. In conclusion, based on our previous clinicopathological analyses and the current study, we suggest that the VDR can function as a melanoma tumor suppressor gene.

【 授权许可】

Unknown