Open AccessUpregulation of adipocyte enhancer‐binding protein 1 in endothelial cells promotes tumor angiogenesis in colorectal cancer
Author(s) -
Yorozu Akira,
Yamamoto Eiichiro,
Niinuma Takeshi,
Tsuyada Akihiro,
Maruyama Reo,
Kitajima Hiroshi,
Numata Yuto,
Kai Masahiro,
Sudo Gota,
Kubo Toshiyuki,
Nishidate Toshihiko,
Okita Kenji,
Takemasa Ichiro,
Nakase Hiroshi,
Sugai Tamotsu,
Takano Kenichi,
Suzuki Hiromu
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14360
Subject(s) - angiogenesis , downregulation and upregulation , periostin , cancer research , gene knockdown , chemistry , biology , cell culture , microbiology and biotechnology , biochemistry , gene , genetics , extracellular matrix
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.