Methionine aminopeptidase-2 is a pivotal regulator of vasculogenic mimicry

Shota Shimizu, Ryota Kawahara, Siro Simizu

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Vasculogenic mimicry (VM) is the formation of a blood supply system that confers aggressive and metastatic properties to tumors and correlates with a poor prognosis in cancer patients. Thus, the inhibition of VM is considered an effective approach for cancer treatment, although such a mechanism remains poorly described. In the present study, we examined methionine aminopeptidase-2 (MetAP2), a key factor of angiogenesis, and demonstrated that it is pivotal for VM, using pharmacological and genetic approaches. Fumagillin and TNP-470, angiogenesis inhibitors that target MetAP2, significantly suppressed VM in various human cancer cell lines. We established MetAP2-knockout (KO) human fibrosarcoma HT1080 cells using the CRISPR/Cas9 system and found that VM was attenuated in these cells. Furthermore, re-expression of wild-type MetAP2 restored VM in the MetAP2-KO HT1080 cells, but the substitution of D251, a conserved amino acid in MetAP2, failed to rescue the VM. Collectively, our results demonstrate that MetAP2 is critical for VM in human cancer cells and suggest fumagillin and TNP-470 as potent VM-suppressing agents.

Original languageEnglish
Article number8242
JournalOncology reports
Volume47
Issue number2
DOIs
Publication statusPublished - 2022 Feb

Keywords

  • Angiogenesis inhibitor
  • Cell migration
  • Fumagillin
  • MetAP2
  • Methionine aminopeptidase-2
  • TNP-470
  • Vasculogenic mimicry

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Methionine aminopeptidase-2 is a pivotal regulator of vasculogenic mimicry'. Together they form a unique fingerprint.

Cite this