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Tumor angiogenesis is an important therapeutic target in colorectal cancer (CRC). We aimed to identify novel genes associated with angiogenesis in CRC. Using RNA sequencing analysis in normal and tumor endothelial cells (TECs) isolated from primary CRC tissues, we detected frequent upregulation of adipocyte enhancer‐binding protein 1 ( AEBP1 ) in TECs. Immunohistochemical analysis revealed that AEBP1 is upregulated in TECs and stromal cells in CRC tissues. Quantitative RT‐PCR analysis showed that there is little or no  AEBP1  expression in CRC cell lines, but that  AEBP1  is well expressed in vascular endothelial cells. Levels of  AEBP1  expression in Human umbilical vein endothelial cells (HUVECs) were upregulated by tumor conditioned medium derived from CRC cells or by direct coculture with CRC cells. Knockdown of  AEBP1  suppressed proliferation, migration, and in vitro tube formation by HUVECs. In xenograft experiments,  AEBP1  knockdown suppressed tumorigenesis and microvessel formation. Depletion of AEBP1 in HUVECs downregulated a series of genes associated with angiogenesis or endothelial function, including aquaporin 1 ( AQP1 ) and periostin ( POSTN ), suggesting that AEBP1 might promote angiogenesis through regulation of those genes. These results suggest that upregulation of AEBP1 contributes to tumor angiogenesis in CRC, which makes AEBP1 a potentially useful therapeutic target.

Upregulation of adipocyte enhancer‐binding protein 1 in endothelial cells promotes tumor angiogenesis in colorectal cancer