Foxc2 transcription factor as a regulator of angiogenesis via induction of integrin beta3 expression.
Angiogenesis, the growth of new blood vessels from pre-existing vessels, is a process involving endothelial cell proliferation, migration and vascular tube formation. One of the key molecules that regulate this process is the integrin beta3 subunit, a cell adhesion receptor that forms a heterodimer with the integrin alphav subunit and interacts with extracellular matrix components such as fibronectin and vitronectin. Although the integrin beta3 subunit is not normally expressed in quiescent endothelial cells, its expression increases in pathological and physiological angiogenesis, including the vasculature in the ischemic tissues such as tumors. Therefore, the integrin beta3 subunit is known to be a potential target for cancer therapy to block tumor angiogenesis. However, the molecular mechanisms for the transcriptional regulation of this subunit are not fully understood. Recently, we reported that Forkhead transcription factor Foxc2 directly induces expression of the integrin beta3 subunit thorough Forkhead-binding elements in its promoter, thereby regulating integrin beta3-mediated endothelial cell migration and adhesion. Thus, our work now identifies Foxc2 as a novel regulator of angiogenesis. In this commentary, we summarize our new findings and discuss prospects for future research in Foxc2-mediated angiogenesis.
Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-6300, USA.
Hisaki
H
Hayashi
Tsutomu
T
Kume
D000818:Animals; D002319:Cardiovascular System / Q000254:growth & development / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism*; D042583:Lymphangiogenesis; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000378:metabolism; D018919:Neovascularization, Physiologic; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D051858:Forkhead Transcription Factors; D039661:Integrin beta3; C082078:mesenchyme fork head 1 protein; D040301:Vascular Endothelial Growth Factor Receptor-2