PTEN: A novel target for vitamin D in melanoma

Artur Shariev; Nicole Painter; Vivienne E Reeve; Nikolas K Haass; Mark S Rybchyn; Furkan A Ince; Rebecca S Mason; Katie M Dixon

doi:10.1016/j.jsbmb.2022.106059

PTEN: A novel target for vitamin D in melanoma

J Steroid Biochem Mol Biol. 2022 Apr:218:106059. doi: 10.1016/j.jsbmb.2022.106059. Epub 2022 Jan 13.

Authors

Artur Shariev¹, Nicole Painter¹, Vivienne E Reeve², Nikolas K Haass³, Mark S Rybchyn⁴, Furkan A Ince¹, Rebecca S Mason⁵, Katie M Dixon⁶

Affiliations

¹ Discipline of Anatomy and Histology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales 2006, Australia.
² Faculty of Veterinary Science, The University of Sydney, New South Wales 2006, Australia.
³ The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Queensland 4102, Australia.
⁴ School of Chemical Engineering, University of New South Wales, Sydney, New South Wales 2033, Australia.
⁵ School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, New South Wales 2006, Australia.
⁶ Discipline of Anatomy and Histology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales 2006, Australia. Electronic address: katie.dixon@sydney.edu.au.

PMID: 35033661
DOI: 10.1016/j.jsbmb.2022.106059

Abstract

Melanoma is the most dangerous form of skin cancer, with poor prognosis in advanced stages. Vitamin D, also produced by ultraviolet radiation, is known for its anti-proliferative properties in some cancers including melanoma. While vitamin D deficiency has been associated with advanced melanoma stage and higher levels of vitamin D have been associated with better outcomes, the role for vitamin D in melanoma remains unclear. Vitamin D synthesis is initiated upon UVB exposure of skin cells and results in formation of the active metabolite 1,25-dihydroxyvitamin D3 (1,25D). We have previously demonstrated that 1,25D plays a role in protection against ultraviolet radiation-induced DNA damage, immune suppression, and skin carcinogenesis. In this study 1,25D significantly reduced cell viability and increased caspase levels in human melanoma cell lines. This effect was not present in cells that lacked both phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a well-known tumour suppressor, and the vitamin D receptor (VDR). PTEN is frequently lost or mutated in melanoma. Incubation of selected melanoma cell lines with 1,25D resulted in significant increases in PTEN levels and downregulation of the AKT pathway and its downstream effectors. This suggests that 1,25D may act to reduce melanoma cell viability by targeting PTEN.

Keywords: 1,25-dihydroxyvitamin D3; AKT; Melanoma; PTEN; Vitamin D receptor; Vitamin D3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Melanoma* / metabolism
PTEN Phosphohydrolase / genetics
Receptors, Calcitriol / genetics
Receptors, Calcitriol / metabolism
Skin Neoplasms* / metabolism
Ultraviolet Rays
Vitamin D
Vitamins

Substances

Receptors, Calcitriol
Vitamins
Vitamin D
PTEN Phosphohydrolase
PTEN protein, human