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Abstract
Angiogenesis is crucial for hepatocellular carcinoma (HCC) development. This study found that sphingosine-1-phosphate receptor 1 (S1PR1) is highly expressed in HCC blood vessels and promotes HCC angiogenesis and progression in vitro and in vivo. Mechanistically, HCC-derived proangiogenic factors (S1P, IL-6, VEGFA) upregulate S1PR1 in endothelial cells (ECs) via STAT3 phosphorylation. S1PR1 decreases ceramide levels by downregulating CerS3 through CerS6 nuclear translocation. Lenvatinib significantly downregulates S1PR1, enhancing angiogenesis inhibition. Therefore, S1PR1 is a promising therapeutic target for HCC.
Publisher
Cell Death and Disease
Published On
Sep 06, 2022
Authors
Xuehong Wang, Zhidong Qiu, Wei Dong, Zebin Yang, Junnan Wang, Hailiang Xu, Tian Sun, Zhaoquan Huang, Junfei Jin
Tags
angiogenesis
hepatocellular carcinoma
S1PR1
vascular development
therapeutic target
STAT3
lenvatinib

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