1st Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
1st Department of Dermatology-Venereology, "Andreas Syggros" Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Exp Dermatol. 2022 Oct;31(10):1466-1476. doi: 10.1111/exd.14653. Epub 2022 Aug 7.
Dual-specificity phosphatase 3 (DUSP3), also known as Vaccinia H1-related phosphatase, is a protein tyrosine phosphatase that typically performs its major role in the regulation of multiple cellular functions through the dephosphorylation of its diverse and constantly expanding range of substrates. Many of the substrates described so far as well as alterations in the expression or the activity of DUSP3 itself are associated with the development and progression of various types of neoplasms, indicating that DUSP3 may be an important player in oncogenesis and a promising therapeutic target. This review focuses exclusively on DUSP3's contribution to either benign or malignant melanocytic oncogenesis, as many of the established culprit pathways and mechanisms constitute DUSP3's regulatory targets, attempting to synthesize the current knowledge on the matter. The spectrum of the DUSP3 interactions analysed in this review covers substrates implicated in cellular growth, cell cycle, proliferation, survival, apoptosis, genomic stability/repair, adhesion and migration of tumor melanocytes. Furthermore, the speculations raised, based on the evidence to date, may be considered a fundament for potential research regarding the oncogenesis, evolution, management and therapeutics of melanocytic tumors.
双特异性磷酸酶 3（DUSP3），也称为牛痘 H1 相关磷酸酶，是一种蛋白酪氨酸磷酸酶，通常通过去磷酸化其广泛且不断扩大的底物范围来调节多种细胞功能，从而发挥其主要作用。迄今为止描述的许多底物以及 DUSP3 本身的表达或活性改变都与各种类型肿瘤的发生和发展有关，这表明 DUSP3 可能是致癌作用中的重要参与者和有前途的治疗靶点。这篇综述专门关注 DUSP3 对良性或恶性黑素细胞肿瘤发生的贡献，因为许多已确立的罪魁祸首途径和机制构成了 DUSP3 的调节靶点，试图综合目前关于这一问题的知识。本综述分析的 DUSP3 相互作用谱涵盖了参与细胞生长、细胞周期、增殖、存活、凋亡、基因组稳定性/修复、肿瘤黑素细胞黏附和迁移的底物。此外，根据迄今为止的证据提出的推测，可以被认为是关于黑素细胞瘤的致癌作用、进化、管理和治疗的潜在研究的基础。
