Medicine and Health

S1PR1 induces metabolic reprogramming of ceramide in vascular endothelial cells, affecting hepatocellular carcinoma angiogenesis and progression

X. Wang, Z. Qiu, et al.

Explore the groundbreaking findings of Xuehong Wang and colleagues as they unveil the pivotal role of S1PR1 in angiogenesis and the progression of hepatocellular carcinoma (HCC). This research reveals how S1PR1's regulation can be a key therapeutic target, offering hope in the fight against HCC. Discover the exciting mechanisms that put S1PR1 at the forefront of new cancer therapies.

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Playback language: English

Index

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

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