Polo-like kinases and UV-induced skin carcinogenesis: What we know and what's next

Abstract

Prolonged and chronic exposure to UV radiation is a risk factor for multiple skin cancers. As the incidence of UV-associated skin cancers continues to rise, there is a pressing need for a deeper understanding of the underlying mechanisms driving these pathologies. Polo-like kinases (PLKs), a family of enzymes consisting of five members (PLK1-PLK5), have been implicated in various aspects of skin carcinogenesis. The inhibition of PLKs is currently being explored as a potential strategy for cancer management. While much of the research has predominantly concentrated on PLK1, recent studies are increasingly shedding light on the role of other PLK family members, given their growing importance in cancer progression. Understanding the relationship between UV-associated skin cancers and PLKs could open new avenues for more effective management of skin cancers. In this review, we discuss the critical mechanisms associated with UV and PLKs in causing skin cancers, followed by the potential role of UV in modulating PLKs in different skin cancers. We also examine the prospect of targeting PLK signaling to enhance therapies for UV-induced skin cancer and improve patient responses. So far, there is not enough literature focused on the simultaneous effects of PLKs and UV using skin cancer models, emphasizing the need for further research to completely understand the role of PLKs in UV-induced skin carcinogenesis.

Keywords: DNA damage; melanoma; polo‐like kinases; skin cancer; ultraviolet radiation.

FIGURE 1

Effects of UV radiation and PLKs in skin cancer. (A) Effects of UV radiation on skin cancer: The key deleterious effects of UV on skin, including mutations and oxidative stress, which may lead to skin cancer are illustrated. (B) Effects of deregulated PLKs in skin cancer: Some of the effects of deregulated PLKs that can cause skin cancer are highlighted. The figure is created in BioRender.

FIGURE 2

Interplay of UV radiation and PLKs in skin cancer. The PLK family plays distinct and important roles in cancer. PLK1 and PLK4 are frequently upregulated in various cancers, including skin cancers, and are associated with enhanced proliferation and tumor progression, whereas PLK5 is typically downregulated and may function as a tumor suppressor. While the roles of PLK2 and PLK3 in skin cancer remain poorly understood, emerging research suggests that they warrant further investigation due to their potential involvement in skin cancer. Ultraviolet (UV) radiation is a well-established driver of skin cancer, and interactions between UV exposure and PLK family members have been observed in other cancer types and normal tissues, mediated through several key signaling pathways (shown in green). Although the specific interplay between UV and PLKs in the context of skin cancer has not been fully elucidated, we speculate that similar signaling axes may be dysregulated in skin cancer cells, potentially contributing to uncontrolled cell proliferation and metastasis. Solid arrow lines show known roles, and dotted arrows show probable roles that need to be validated. The figure is created in BioRender.