Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
Int J Mol Sci. 2024 Jun 22;25(13):6868. doi: 10.3390/ijms25136868.
Tumor angiogenesis, the formation of new blood vessels to support tumor growth and metastasis, is a complex process regulated by a multitude of signaling pathways. Dysregulation of signaling pathways involving protein kinases has been extensively studied, but the role of protein phosphatases in angiogenesis within the tumor microenvironment remains less explored. However, among angiogenic pathways, protein phosphatases play critical roles in modulating signaling cascades. This review provides a comprehensive overview of the involvement of protein phosphatases in tumor angiogenesis, highlighting their diverse functions and mechanisms of action. Protein phosphatases are key regulators of cellular signaling pathways by catalyzing the dephosphorylation of proteins, thereby modulating their activity and function. This review aims to assess the activity of the protein tyrosine phosphatases and serine/threonine phosphatases. These phosphatases exert their effects on angiogenic signaling pathways through various mechanisms, including direct dephosphorylation of angiogenic receptors and downstream signaling molecules. Moreover, protein phosphatases also crosstalk with other signaling pathways involved in angiogenesis, further emphasizing their significance in regulating tumor vascularization, including endothelial cell survival, sprouting, and vessel maturation. In conclusion, this review underscores the pivotal role of protein phosphatases in tumor angiogenesis and accentuate their potential as therapeutic targets for anti-angiogenic therapy in cancer.
肿瘤血管生成,即新血管的形成以支持肿瘤生长和转移,是一个受多种信号通路调控的复杂过程。涉及蛋白激酶的信号通路失调已得到广泛研究,但蛋白磷酸酶在肿瘤微环境中的血管生成中的作用仍较少被探索。然而,在血管生成途径中,蛋白磷酸酶在调节信号级联中起着关键作用。这篇综述全面概述了蛋白磷酸酶在肿瘤血管生成中的作用,强调了它们的多种功能和作用机制。蛋白磷酸酶通过催化蛋白质的去磷酸化来调节细胞信号通路,从而调节其活性和功能。本综述旨在评估蛋白酪氨酸磷酸酶和丝氨酸/苏氨酸磷酸酶的活性。这些磷酸酶通过多种机制发挥其对血管生成信号通路的作用,包括直接去磷酸化血管生成受体和下游信号分子。此外,蛋白磷酸酶还与其他参与血管生成的信号通路相互作用,进一步强调了它们在调节肿瘤血管生成中的重要性,包括内皮细胞存活、发芽和血管成熟。总之,本综述强调了蛋白磷酸酶在肿瘤血管生成中的关键作用,并强调了它们作为癌症抗血管生成治疗的治疗靶点的潜力。