Soluble E-cadherin promotes tumor angiogenesis and localizes to exosome surface

Maggie K.S. Tang, Patrick Y.K. Yue, Philip P. Ip, Rui Lan Huang, Hung Cheng Lai, Annie N.Y. Cheung, Ka Yu Tse, Hextan Y.S. Ngan, Alice S.T. Wong

研究成果: 雜誌貢獻文章

38 引文 斯高帕斯(Scopus)

摘要

The limitations of current anti-angiogenic therapies necessitate other targets with complimentary mechanisms. Here, we show for the first time that soluble E-cadherin (sE-cad) (an 80-kDa soluble form), which is highly expressed in the malignant ascites of ovarian cancer patients, is a potent inducer of angiogenesis. In addition to ectodomain shedding, we provide further evidence that sE-cad is abundantly released in the form of exosomes. Mechanistically, sE-cad-positive exosomes heterodimerize with VE-cadherin on endothelial cells and transduce a novel sequential activation of β-catenin and NFκB signaling. In vivo and clinical data prove the relevance of sE-cad-positive exosomes for malignant ascites formation and widespread peritoneal dissemination. These data advance our understanding of the molecular regulation of angiogenesis in ovarian cancer and support the therapeutic potential of targeting sE-cad. The exosomal release of sE-cad, which represents a common route for externalization in ovarian cancer, could potentially be biomarkers for diagnosis and prognosis.
原文英語
文章編號2270
期刊Nature Communications
9
發行號1
DOIs
出版狀態已發佈 - 十二月 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Tang, M. K. S., Yue, P. Y. K., Ip, P. P., Huang, R. L., Lai, H. C., Cheung, A. N. Y., Tse, K. Y., Ngan, H. Y. S., & Wong, A. S. T. (2018). Soluble E-cadherin promotes tumor angiogenesis and localizes to exosome surface. Nature Communications, 9(1), [2270]. https://doi.org/10.1038/s41467-018-04695-7