TY - JOUR
T1 - Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature
AU - Hooglugt, Aukie
AU - van der Stoel, Miesje M.
AU - Boon, Reinier A.
AU - Huveneers, Stephan
N1 - Funding Information: This study was financially supported by the Netherlands Organization of Scientific Research (NWO-VIDI grant 016.156.327) and the Amsterdam Cardiovascular Sciences institute. Publisher Copyright: © Copyright © 2021 Hooglugt, van der Stoel, Boon and Huveneers.
PY - 2021/2/4
Y1 - 2021/2/4
N2 - 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.
AB - 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.
KW - Angiogenic therapy
KW - TAZ
KW - cancer
KW - endothelium
KW - mechanotransduction
KW - tumor angiogenesis
KW - tumor vasculature
KW - yes-associated protein (YAP)
UR - http://www.scopus.com/inward/record.url?scp=85101188596&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85101188596&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/33614496
U2 - https://doi.org/10.3389/fonc.2020.612802
DO - https://doi.org/10.3389/fonc.2020.612802
M3 - Review article
C2 - 33614496
SN - 2234-943X
VL - 10
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 612802
ER -