Department of Anesthesiology, Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia (UBC), 2176 Health Sciences mall, room 217, Vancouver, BC, V6T 1Z3, Canada.
Centre for Heart & Lung Innovation, St. Paul's Hospital, Vancouver, Canada.
Cancer Metastasis Rev. 2020 Jun;39(2):471-483. doi: 10.1007/s10555-020-09895-6.
Since the initial reports implicating caveolin-1 (CAV1) in neoplasia, the scientific community has made tremendous strides towards understanding how CAV1-dependent signaling and caveolae assembly modulate solid tumor growth. Once a solid neoplastic tumor reaches a certain size, it will increasingly rely on its stroma to meet the metabolic demands of the rapidly proliferating cancer cells, a limitation typically but not exclusively addressed via the formation of new blood vessels. Landmark studies using xenograft tumor models have highlighted the importance of stromal CAV1 during neoplastic blood vessel growth from preexisting vasculature, a process called angiogenesis, and helped identify endothelium-specific signaling events regulated by CAV1, such as vascular endothelial growth factor (VEGF) receptors as well as the endothelial nitric oxide (NO) synthase (eNOS) systems. This chapter provides a glimpse into the signaling events modulated by CAV1 and its scaffolding domain (CSD) during endothelial-specific aspects of neoplastic growth, such as vascular permeability, angiogenesis, and mechanotransduction.
自最初有研究报告将窖蛋白-1（CAV1）与肿瘤发生联系起来以来，科学界在理解 CAV1 依赖性信号转导和小窝组装如何调节实体瘤生长方面取得了巨大进展。一旦实体瘤达到一定大小，它将越来越依赖基质来满足快速增殖的癌细胞的代谢需求，这种限制通常但并非排他性地通过形成新的血管来解决。使用异种移植肿瘤模型的开创性研究强调了基质 CAV1 在从现有脉管系统开始的肿瘤血管生长过程中的重要性，这个过程称为血管生成，并帮助确定了由 CAV1 调节的内皮细胞特异性信号事件，例如血管内皮生长因子（VEGF）受体以及内皮型一氧化氮合酶（eNOS）系统。本章简要介绍了 CAV1 及其支架结构域（CSD）在肿瘤生长的内皮特异性方面调节的信号事件，如血管通透性、血管生成和机械转导。
