Mechanical Stress as a Pathomechanism of Plantar Acral Melanoma

Sun exposure is widely recognized as a major etiologic factor in cutaneous melanoma. However, melanomas also occur in skin areas unexposed to the sun, such as the palmoplantar surface. Although the risk factors and mutational processes underlying acral melanoma remain poorly understood, these tumors frequently occur at sites of increased mechanical stress on the hand and foot, suggesting that mechanical stress may contribute to the development of plantar melanoma. Furthermore, mechanical forces regulate skin homeostasis, especially during skin development, regeneration, and wound healing. In plantar acral melanoma, mechanical stress associated with weight-bearing activity has been linked to nuclear membrane instability, which may explain the frequent occurrence of plantar acral melanoma at higher mechanical stress points. In this review, we discuss the role of mechanical stress in melanoma pathogenesis and provide an overview of mechanobiological mechanisms involved in melanoma progression and aggressiveness. Insights from these investigations may guide future research and improve the management of acral melanoma.