Akil Abdellah, Gutiérrez-García Ana K, Guenter Rachael, Rose J Bart, Beck Adam W, Chen Herbert, Ren Bin
Department of Surgery, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
O'Neal Comprehensive Cancer Center, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Front Cell Dev Biol. 2021 Feb 16;9:642352. doi: 10.3389/fcell.2021.642352. eCollection 2021.
The Notch signaling pathway plays an essential role in a wide variety of biological processes including cell fate determination of vascular endothelial cells and the regulation of arterial differentiation and angiogenesis. The Notch pathway is also an essential regulator of tumor growth and survival by functioning as either an oncogene or a tumor suppressor in a context-dependent manner. Crosstalk between the Notch and other signaling pathways is also pivotal in tumor progression by promoting cancer cell growth, migration, invasion, metastasis, tumor angiogenesis, and the expansion of cancer stem cells (CSCs). In this review, we provide an overview and update of Notch signaling in endothelial cell fate determination and functioning, angiogenesis, and tumor progression, particularly in the development of CSCs and therapeutic resistance. We further summarize recent studies on how endothelial signaling crosstalk with the Notch pathway contributes to tumor angiogenesis and the development of CSCs, thereby providing insights into vascular biology within the tumor microenvironment and tumor progression.
Notch信号通路在多种生物学过程中发挥着至关重要的作用，包括血管内皮细胞的细胞命运决定以及动脉分化和血管生成的调节。Notch通路还通过在不同背景下作为癌基因或肿瘤抑制基因发挥作用，成为肿瘤生长和存活的重要调节因子。Notch与其他信号通路之间的相互作用在肿瘤进展中也起着关键作用，可促进癌细胞的生长、迁移、侵袭、转移、肿瘤血管生成以及癌症干细胞（CSC）的扩增。在本综述中，我们概述并更新了Notch信号通路在内皮细胞命运决定与功能、血管生成以及肿瘤进展方面的研究，特别是在CSC的发展和治疗抗性方面。我们进一步总结了关于内皮信号与Notch通路相互作用如何促进肿瘤血管生成和CSC发展的最新研究，从而为肿瘤微环境中的血管生物学和肿瘤进展提供见解。
