Keratinocyte organelle reprogramming as a key player in melanocyte biology in health and disease

Abstract

Melanoma, an aggressive skin cancer, poses significant global health challenges due to its increasing incidence and high metastatic potential. While traditionally focused on genetic mutations, recent research highlights the critical role of cellular organelle dysfunction and intricate inter-organelle communication in both keratinocytes and melanocytes during melanoma pathogenesis. This systematic review explores how alterations within key organelles, including mitochondria, endoplasmic reticulum (ER), Golgi apparatus, lysosomes, peroxisomes, and lamellar bodies. reprogram cellular behavior and contribute to disease progression. We detail how mitochondrial dysfunction and elevated reactive oxygen species (ROS) levels in keratinocytes can prime the microenvironment for melanocyte transformation. Lysosomes and peroxisomes, vital for degradation, lipid metabolism, and redox balance, when compromised, impair cellular differentiation and oxidative stress management, fostering a pro-tumorigenic state. The ER and ribosomes, crucial for protein synthesis and quality control, are frequently impacted by environmental stressors like UV radiation, leading to adaptive or detrimental cellular responses. Furthermore, the proper function of lamellar bodies, essential for skin barrier integrity, is intrinsically linked to Golgi and lysosomal health, with disruptions influencing melanoma dissemination. Understanding the complex interplay and dysregulation of these organelles offers a multifaceted perspective on melanoma, moving beyond isolated cellular events to reveal systemic imbalances. This review underscores the potential for developing novel strategies that target specific organelle pathways, aiming to restore cellular homeostasis and effectively combat tumor progression.