Methionine aminopeptidase-2 is a pivotal regulator of vasculogenic mimicry

Shota Shimizu, Ryota Kawahara, Siro Simizu

研究成果: Article査読

4 被引用数 (Scopus)


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.

ジャーナルOncology reports
出版ステータスPublished - 2022 2月

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究


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