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Cancer Res. 2009 Apr 15;69(8):3272-7. doi: 10.1158/0008-5472.CAN-08-4886. Epub 2009 Apr 7.

The L6 protein TM4SF1 is critical for endothelial cell function and tumor angiogenesis.

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Center for Vascular Biological Research and Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.


Transmembrane-4-L-six-family-1 (TM4SF1) was originally described as a cancer cell protein. Here, we show that it is highly expressed in the vascular endothelium of human cancers and in a banded pattern in the filopodia of cultured endothelial cells (EC). TM4SF1 knockdown prevented filopodia formation, inhibited cell mobility, blocked cytokinesis, and rendered EC senescent. Integrin-alpha5 and integrin-beta1 subunits gave a similar staining pattern and interacted constitutively with TM4SF1, whereas integrin subunits often associated with angiogenesis (alphaV, beta3, beta5) interacted with TM4SF1 only after vascular endothelial growth factor (VEGF)-A or thrombin stimulation. TM4SF1 knockdown substantially inhibited maturation of VEGF-A(164)-induced angiogenesis. Thus, TM4SF1 is a key regulator of EC function in vitro and of pathologic angiogenesis in vivo and is potentially an attractive target for antiangiogenesis therapy.

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