ANGPTL4 is a secreted tumor suppressor that inhibits angiogenesis

E. Okochi-Takada, N. Hattori, T. Tsukamoto, K. Miyamoto, T. Ando, S. Ito, Y. Yamamura, M. Wakabayashi, Y. Nobeyama, T. Ushijima

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Tumor suppressors with extracellular function are likely to have advantages as targets for cancer therapy, but few are known. Here, we focused on angiopoietin-like 4 (ANGPTL4), which is a secreted glycoprotein involved in lipoprotein metabolism and angiogenesis, is methylation-silenced in human cancers, but has unclear roles in cancer development and progression. We found a deletion mutation in its coiled-coil domain at its N-terminal in human gastric cancers, in addition to hypermethylation of the ANGPTL4 promoter CpG islands. Forced expression of wild-type ANGPTL4, but not ANGPTL4 with the deletion, at physiological levels markedly suppressed in vivo tumorigenicity and tumor angiogenesis, indicating that the latter caused the former. Tumor-derived ANGPTL4 suppressed in vitro vascular tube formation and proliferation of human umbilical vascular endothelial cells, partly due to suppression of ERK signaling. These showed that ANGPTL4 is a genetically and epigenetically inactivated secreted tumor suppressor that inhibits tumor angiogenesis.

Original languageEnglish
Pages (from-to)2273-2278
Number of pages6
JournalOncogene
Volume33
Issue number17
DOIs
Publication statusPublished - 24-04-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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