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Integral Role of Transcription Factor 8 in the Negative Regulation of Tumor Angiogenesis

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Title: Integral Role of Transcription Factor 8 in the Negative Regulation of Tumor Angiogenesis
Authors: Inuzuka, Takayuki Browse this author
Tsuda, Masumi Browse this author →KAKEN DB
Tanaka, Shinya Browse this author →KAKEN DB
Kawaguchi, Hideaki Browse this author →KAKEN DB
Higashi, Yujiro Browse this author
Ohba, Yusuke Browse this author →KAKEN DB
Keywords: angiogenesis
tumor angiogenesis
Issue Date: 15-Feb-2009
Publisher: American Association for Cancer Research
Journal Title: Cancer Research
Volume: 69
Issue: 4
Start Page: 1678
End Page: 1684
Publisher DOI: 10.1158/0008-5472.CAN-08-3620
PMID: 19208835
Abstract: Angiogenesis is involved in various physiologic and pathological conditions, including tumor growth, and is tightly regulated by the orchestration of proangiogenic and antiangiogenic factors. Inhibition of vascular endothelial growth factor (VEGF), the best-established antiangiogenic treatment in cancer, has shown some effectiveness; however, the identification of novel regulators, whose function is independent of VEGF, is required to achieve better outcomes. Here, we show that transcription factor 8 (TCF8)is up-regulated in endothelial cells during angiogenesis, acting as a negative regulator. Furthermore, TCF8 is specifically expressed in the endothelium of tumor vessels. Tcf8-heterozygous knockout mice are more permissive than wildtype mice to the formation of tumor blood vessels in s.c. implanted melanoma, which seems to contribute to the more aggressive growth and the lung metastases of the tumor in mutant mice. Suppression of TCF8 facilitates angiogenesis in both in vitro and ex vivo models, and displays comprehensive cellular phenotypes, including enhanced cell invasion, impaired cell adhesion, and increased cell monolayer permeability due to, at least partly, MMP1 overexpression, attenuation of focal adhesion formation, and insufficient VE-cadherin recruitment, respectively. Taken together, our findings define a novel, integral role for TCF8 in the regulation of pathologic angiogenesis, and propose TCF8 as a target for therapeutic intervention in cancer.
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 大場 雄介

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