Skin Cancers and the Contribution of Rho GTPase Signaling Networks to Their Progression

SIMPLE SUMMARY: Skin cancer is the most common cancer in human. Melanoma, basal cell carcinoma and squamous cell carcinoma are the most prevalent skin cancer subtypes. A better understanding of the molecular mechanisms that contribute to the progression of skin cancer is essential due to their prevalence in the population and the emergence of resistance to current treatment for aggressive cases. The aim of our review is to provide an overview of how Rho GTPases and their regulators contribute to skin cancer progression via the perturbation of their function in the skin. ABSTRACT: Skin cancers are the most common cancers worldwide. Among them, melanoma, basal cell carcinoma of the skin and cutaneous squamous cell carcinoma are the three major subtypes. These cancers are characterized by different genetic perturbations even though they are similarly caused by a lifelong exposure to the sun. The main oncogenic drivers of skin cancer initiation have been known for a while, yet it remains unclear what are the molecular events that mediate their oncogenic functions and that contribute to their progression. Moreover, patients with aggressive skin cancers have been known to develop resistance to currently available treatment, which is urging us to identify new therapeutic opportunities based on a better understanding of skin cancer biology. More recently, the contribution of cytoskeletal dynamics and Rho GTPase signaling networks to the progression of skin cancers has been highlighted by several studies. In this review, we underline the various perturbations in the activity and regulation of Rho GTPase network components that contribute to skin cancer development, and we explore the emerging therapeutic opportunities that are surfacing from these studies.