Mechanics of PAK1—A new molecular player in the arena of skin cancer

Abstract

Despite regular exposure of skin to solar UV-B irradiation, most individuals enjoy cancer-free existence, which is a testimony of the inherent capacity of human keratinocytes to either repair or restore cells damged by UV exposure. In this manuscript, we focus on delineating the mechanistic role of p21 activated kinase (Pak1) in UV-B provoked skin lesions. Molecular mechanistic studies revealed that Pak1 is triggered as a consequence to UV-B exposure via epidermal growth factor receptor (EGFR) and cyclobutane pyrimidine dimers (CPD) pathways, and both these membranous (EGFR) and nuclear (CPDs) events converge at Pak1 activation and contribute in a coordinated manner for yielding a complete response to UV-B via upregulating Ataxia–Telangiectasia and Rad3 related (ATR). This is the first study that evaluates the mechanistic role of a signaling molecule, Pak1, in premalignant skin lesions caused by sun exposure and designate that expression and instigation of Pak1 could operate as an alarming indicator of succession towards aggressive form of skin cancer, if neglected.