CSPG4, a potential therapeutic target, facilitates malignant progression of melanoma.
CSPG4, a potential therapeutic target, facilitates malignant progression of melanoma.
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DOI：
10.1111/j.1755-148x.2011.00929.x
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发表时间：
2011-12
影响因子：
4.3
通讯作者：
McCarthy JB
中科院分区：
文献类型：
--
作者：
Price MA;Colvin Wanshura LE;Yang J;Carlson J;Xiang B;Li G;Ferrone S;Dudek AZ;Turley EA;McCarthy JB
硫酸软骨素蛋白多糖 4 (CSPG4) 是一种跨膜蛋白多糖，最初被鉴定为黑色素瘤细胞表面的高度免疫原性肿瘤抗原，与黑色素瘤肿瘤的形成以及某些黑色素瘤和其他几种肿瘤类型的不良预后相关。 CSPG4 影响黑色素瘤进展的复杂机制已经开始被明确，特别是与其他细胞表面蛋白和受体酪氨酸激酶 (RTK) 的关联及其在调节这些蛋白功能中的核心作用。 CSPG4 通过调节整合素功能和增强生长因子受体调节途径（包括持续激活 ERK 1,2），对黑色素瘤的生长至关重要。 CSPG4 对整合素、RTK 和 ERK 1,2 功能的激活可调节肿瘤进展的许多方面。 CSPG4 表达进一步与黑色素瘤对传统化疗药物的耐药性相关。这篇综述概述了我们对 CSPG4 相关细胞信号传导理解的最新进展，描述了它在黑色素瘤肿瘤细胞生长、运动和存活中发挥的核心作用，并探讨了改变 CSPG4 功能和蛋白质-蛋白质相互作用如何为我们提供治疗晚期黑色素瘤的新型组合疗法。
Chondroitin sulfate proteoglycan 4 (CSPG4), a transmembrane proteoglycan originally identified as a highly immunogenic tumor antigen on the surface of melanoma cells, is associated with melanoma tumor formation and poor prognosis in certain melanomas and several other tumor types. The complex mechanisms by which CSPG4 affects melanoma progression have started to be defined, in particular the association with other cell surface proteins and receptor tyrosine kinases (RTKs) and its central role in modulating the function of these proteins. CSPG4 is essential to the growth of melanoma tumors through its modulation of integrin function and enhanced growth factor receptor-regulated pathways including sustained activation of ERK 1,2. This activation of integrin, RTK, and ERK 1,2 function by CSPG4 modulates numerous aspects of tumor progression. CSPG4 expression has further been correlated to resistance of melanoma to conventional chemotherapeutics. This review outlines recent advances in our understanding of CSPG4-associated cell signaling, describing the central role it plays in melanoma tumor cell growth, motility, and survival, and explores how modifying CSPG4 function and protein–protein interactions may provide us with novel combinatorial therapies for the treatment of advanced melanoma.