Vasohibin-2 is required for epithelial–mesenchymal transition of ovarian cancer cells by modulating transforming growth factor-β signaling

Rie Norita, Yasuhiro Suzuki, Yutaka Furutani, Kazuki Takahashi, Yasuhiro Yoshimatsu, Katarzyna A. Podyma-Inoue, Tetsuro Watabe, Yasufumi Sato

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Vasohibin-2 (VASH2) is a homolog of VASH1, an endothelium-derived angiogenesis inhibitor. Vasohibin-2 is mainly expressed in cancer cells, and has been implicated in the progression of cancer by inducing angiogenesis and tumor growth. Although VASH2 has been recently reported to be involved in epithelial–mesenchymal transition (EMT), its precise roles are obscure. The aim of the present study was to clarify the role of VASH2 in the EMT of cancer cells in relation to transforming growth factor-β (TGF-β) signaling, which is a major stimulator of EMT. Decreased expression of VASH2 in ovarian cancer cells significantly repressed the expression of TGF-β type I receptor, namely activin receptor-like kinase 5. Transforming growth factor-β1-induced phosphorylation of Smad2 and Smad3 was markedly decreased in VASH2 knockdown cells while the expression of Smad2 and Smad3 was unchanged. Accordingly, the responses to TGF-β1 shown by promoter assay and plasminogen activator inhibitor type 1 expression were significantly attenuated in VASH2 knockdown cells. Furthermore, knockdown of VASH2 in cancer cells abrogated the TGF-β1-induced reduced expression of epithelial markers including E-cadherin, and the elevated expression of mesenchymal markers including fibronectin, ZEB2, and Snail2, suggesting that endogenous VASH2 is required for TGF-β1-induced EMT. In accordance with these results, the effects of TGF-β1 on cell morphology, migration, invasion, and MMP2 expression were also abrogated when VASH2 was knocked down. These results indicate that VASH2 played a significant role in the EMT by modulating the TGF-β signaling. We propose that VASH2 would be a novel molecular target for the prevention of EMT in cancers.

Original languageEnglish
Pages (from-to)419-426
Number of pages8
JournalCancer science
Issue number3
Publication statusPublished - 2017 Mar 1


  • ALK5
  • EMT
  • TGF-β
  • ovarian cancer
  • vasohibin-2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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