YAP1 Inhibition in HUVECs Is Associated with Released Exosomes and Increased Hepatocarcinoma Invasion and Metastasis

Molecular Therapy. Nucleic Acids
Yan LiJingang Liu

Abstract

Hepatocellular carcinoma is one of the most common gastrointestinal malignancies. Anti-angiogenesis therapies have recently demonstrated promise in the treatment of malignancies, although early treatment benefits may be accompanied by metastasis over time. Additional and more effective anti-angiogenic treatment modalities are therefore needed. We previously found that Yes-associated protein 1 (YAP1) expression is increased in hepatocellular carcinoma (HCC), particularly around tumor-associated blood vessels, suggesting a role in angiogenesis. The YAP1 inhibitor verteporfin is presently in anti-angiogenic clinical trials for the treatment of various cancers. Depleted YAP1 from vascular endothelial cells effectively reduced proliferation and tube formation, validating its utility as an anti-angiogenesis target. We also showed that YAP1 depletion or inhibition in vascular endothelial cells leads to increased release of exosomes containing the long non-coding RNA (lncRNA) MALAT1 into the tumor microenvironment. Direct exosomal transfer of MALAT1 to hepatic cells leads to increased hepatic cell invasion and migration via activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. These observations may explain the oc...Continue Reading

Citations

Dec 29, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Yu-Shui MaDa Fu
Dec 29, 2020·Frontiers in Cell and Developmental Biology·Ye Zeng, Bingmei M Fu
Mar 7, 2021·Cancers·Andrés Rincón-RiverosJosefa Antonia Rodriguez
Mar 20, 2021·Frontiers in Cell and Developmental Biology·Alberto Hernández-BarrancoHéctor Peinado
Jun 6, 2021·Journal of Experimental & Clinical Cancer Research : CR·Xueqiang PengHangyu Li
Aug 12, 2021·Molecular Cancer Therapeutics·Wangyang ZhengYunfu Cui
Sep 20, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Xueqiang PengHangyu Li

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Datasets Mentioned

BETA
GSE73396
GSE35004
GSE61989

Methods Mentioned

BETA
PCR
xenograft
transfection
electron microscopy
Confocal microscopy
Assay

Software Mentioned

Click
iT
GEPIA
NanoSight
GSEA
Gene Expression Profiling Interactive Analysis ( GEPIA )
ImageJ

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