4.6 Review

Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature

Journal

FRONTIERS IN ONCOLOGY
Volume 10, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.612802

Keywords

yes-associated protein (YAP); TAZ; tumor vasculature; endothelium; mechanotransduction; cancer; Angiogenic therapy; tumor angiogenesis

Categories

Funding

  1. Netherlands Organization of Scientific Research (NWO-VIDI) [016.156.327]
  2. Amsterdam Cardiovascular Sciences institute

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Solid tumors rely on vascularization for growth, with YAP/TAZ activation playing a crucial role in promoting tumor angiogenesis. Understanding the regulation of endothelial YAP/TAZ and its downstream targets is essential for developing effective anti-cancer therapies. Strategies targeting YAP/TAZ in tumor endothelium and exploring vascular normalization may hold promise for improving tumor treatments.
Solid tumors are dependent on vascularization for their growth. The hypoxic, stiff, and pro-angiogenic tumor microenvironment induces angiogenesis, giving rise to an immature, proliferative, and permeable vasculature. The tumor vessels promote tumor metastasis and complicate delivery of anti-cancer therapies. In many types of tumors, YAP/TAZ activation is correlated with increased levels of angiogenesis. In addition, endothelial YAP/TAZ activation is important for the formation of new blood and lymphatic vessels during development. Oncogenic activation of YAP/TAZ in tumor cell growth and invasion has been studied in great detail, however the role of YAP/TAZ within the tumor endothelium remains insufficiently understood, which complicates therapeutic strategies aimed at targeting YAP/TAZ in cancer. Here, we overview the upstream signals from the tumor microenvironment that control endothelial YAP/TAZ activation and explore the role of their downstream targets in driving tumor angiogenesis. We further discuss the potential for anti-cancer treatments and vascular normalization strategies to improve tumor therapies.

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