Exploring vitamin D signalling within skin cancer

Abstract

Sunlight exposure of the skin is associated with both risks and benefits. On one hand, sunlight ultraviolet (UV) radiation can cause skin cancer through signature DNA mutations. On the other hand, it can be absorbed in the skin by 7‐dehydrocholesterol to instigate endogenous synthesis of vitamin D to regulate anticancer effects. Thus, protecting one's skin from sunlight to avoid skin cancer may lead to impaired vitamin D levels arguing for sensible sun exposure practices. To limit cancer, vitamin D metabolites can promote uncharacterized and diverse sets of events such as repair responses to DNA damage, apoptosis of malignant cells, and suppression of immune surveillance, proliferation and angiogenesis. Recent findings also suggest that part of the anticancer effects of vitamin D within squamous cell carcinoma—a type of skin cancer most directly linked to sun exposure—involves the DDIT4‐mTOR catabolic signalling pathway to enhance cell autophagy. As mTOR activity and cellular metabolism are modulated as part of the DNA damage response, insights into the means by which mTOR can be controlled by vitamin D to suppress cancer is of molecular and clinical importance. Overall, the research so far suggests that presence of vitamin D through sunlight exposure and supplementation are beneficial for human health in the face of cancer.

Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

“…Since vitamin D also exhibits antiproliferative and pro-differentiating properties, its deficiency has been correlated with the progression of several malignancies [ 70 , 215 , 216 , 217 , 218 , 219 ], especially breast [ 220 , 221 , 222 , 223 ], ovarian [ 224 , 225 ] and skin tumours [ 226 , 227 , 228 , 229 ].…”

Vitamin D Regulation of a SOD1-to-SOD2 Antioxidative Switch to Prevent Bone Cancer

“…For example, SOD2 is regulated by SIRT3-mediated deacetylation that can attenuate excessive production of mitochondrial ROS under disease conditions [35]. Vitamin D exerts its anti-cancer effects by a variety of mechanisms [7,10,[36][37][38]. However, only a few studies have looked at the role of vitamin D on ROS production and detoxification.…”

Assessment of sun‑related behavior and serum vitamin D in basal cell carcinoma: Preliminary results

“…UV radiation upregulates Shh pathway, also loss of VDR increases Shh components indicating that VDR might have an antagonistic effect to UV radiation. VDR is most probably protective in the formation of BCC as it may support the regeneration of the skin (21). Vitamin D that is synthetized in the skin can inhibit Shh, whereas dietary vitamin D cannot (22).…”