EGFL6 promotes breast cancer by simultaneously enhancing cancer cell metastasis and stimulating tumor angiogenesis

Jingnan An, Yi Du, Xuejun Fan, Yanhong Wang, Cristina Ivan, Xue Guang Zhang, Anil K. Sood, Zhiqiang An, Ningyan Zhang

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

EGFL6, a member of the EGF-like superfamily, plays an important role during embryonic development and has been implicated in promotion of tumor angiogenesis without affecting wound healing. There is very little known about the function of EGFL6 in cancer cells. Here, we investigated whether EGFL6 plays a direct role in cancer cells in addition to the promotion of tumor angiogenesis. Our study showed that EGFL6 promoted epithelial–mesenchymal transition (EMT) and stemness of breast cancer cells and increased cell migration and invasion in cell culture studies. We also found that EGFL6 reduced apoptotic signaling in cancer cells and promoted tumor growth in vivo. Importantly, expression of EGFL6 in cancer cells and tumor endothelial cells not only increased tumor angiogenesis but also promoted migration of cancer cells. Such dual engagement of cancer and stromal cells suggests crosstalk mediated by EGFL6 in the tumor microenvironment. Blockade of EGFL6 using our novel anti-EGFL6 monoclonal antibody significantly reduced cancer cell migration, tumor angiogenesis, and tumor growth in mouse xenograft tumor models. Silencing EGFL6 mRNA by shRNA transfection of cancer cells also significantly reduced cancer cell migration, tumor angiogenesis, and tumor growth in mouse xenograft tumor models. Taken together, the results of this study indicate that targeting EGFL6 is a unique strategy for inhibiting both cancer cell metastasis and tumor angiogenesis.

Original languageEnglish (US)
Pages (from-to)2123-2134
Number of pages12
JournalOncogene
Volume38
Issue number12
DOIs
StatePublished - Mar 21 2019
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    An, J., Du, Y., Fan, X., Wang, Y., Ivan, C., Zhang, X. G., Sood, A. K., An, Z., & Zhang, N. (2019). EGFL6 promotes breast cancer by simultaneously enhancing cancer cell metastasis and stimulating tumor angiogenesis. Oncogene, 38(12), 2123-2134. https://doi.org/10.1038/s41388-018-0565-9