Mechanical Force and Actin Dynamics during Cutaneous Squamous Cell Carcinoma (cSCC) Progression: Opportunities for Novel Treatment Modalities

Abstract

Cutaneous squamous cell carcinoma (cSCC) accounts for 25% of cutaneous malignancies diagnosed in the Caucasian population. Surgical removal in combination with radio- and chemotherapy is an effective treatment; however, prognosis for patients suffering from aggressive cSCC is still relatively poor. Increasing prevalence coupled with high mortality and morbidity in aggressive metastatic forms of cSCC highlights the need for development of novel targeted therapeutics. Metastasis is a complex process requiring dramatic reorganization of the cell cytoskeleton. Recent studies have highlighted the importance of mechanical forces and actin dynamics in cancer cells’ intrinsic ability to invade adjacent tissues, intravasate into vasculature, and ultimately metastasize. Tight regulation of the biochemical and mechanical properties of the actin cytoskeleton drives cellular processes involved in cSCC progression including polarity establishment, morphogenesis, and motility. Here we will provide a short introduction to disease pathogenesis, give an overview of the role of key regulatory proteins governing the mechanical forces and actin dynamics critical to cSCC progression, and describe the contribution of actin remodeling and actomyosin signaling to cSCC progression. We will also discuss how targeting protein regulating mechanical force and actin dynamics may have clinical utility in development of novel treatment modalities for patients suffering from aggressive cSCC.