title: CD24 promoted cancer cell angiogenesis via Hsp90-mediated STAT3/VEGF signaling pathway in colorectal cancer.
abstract: CD24 is involved in tumor progression of various cancers, but the effects of CD24 on tumor angiogenesis in colorectal cancer are still unknown. We aimed to investigate the underlying mechanism and role of CD24 on colorectal cancer (CRC) angiogenesis. Our data showed that the microvessal density (MVD) was related to the expression of CD24 in primary and metastasis CRC. Silencing of CD24 could dramatically decrease human umbilical vein endothelial cell (HUVEC) migration, invasion and tubule formation, but trivially affected cell proliferation. We also mechanically showed that silencing CD24 could downregulate the expression of VEGF via inhibiting the phosphorylation and translocation of STAT3. Moreover, Hsp90 was identified as the down-interaction protein of CD24 with co-immunoprecipitation assay and systematic mass spectrometry. Immunofluorescence results showed Hsp90 partly co-localized with CD24 in CRC cell membrane and there was a positive correlation between CD24 and Hsp90 expression in CRC tissues. We gradually evidenced that Hsp90 modulated the stability and degradation of CD24 in a proteasome-depended manner, and transferred the signal transmission from CD24 to STAT3. 17-AAG, a specific Hsp90, could abrogate the CD24 induce- HUVEC migration, invasion and tubule formation in vitro and in vivo. Collectively, our results suggested that CD24 induced CRC angiogenesis in Hsp90-dependent manner and activated STAT3-mediated transcription of VEGF. We provided a new insight into the regulation mechanism of tumor angiogenesis by exploring the role of CD24 in angiogenesis.
authors: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|Guangdong Provincial Key Laboratory of Gastroenterology, Guangzhou 510515, China.
authors: Xinying
authors: X
authors: Wang
authors: Department of Gastroenterology, The First People's Hospital of Yunnan Province, Kunming 65003, China.
authors: Yu
authors: Y
authors: Zhang
authors: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|Guangdong Provincial Key Laboratory of Gastroenterology, Guangzhou 510515, China.
authors: Yingying
authors: Y
authors: Zhao
authors: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|Guangdong Provincial Key Laboratory of Gastroenterology, Guangzhou 510515, China.
authors: Yanling
authors: Y
authors: Liang
authors: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|Guangdong Provincial Key Laboratory of Gastroenterology, Guangzhou 510515, China.
authors: Cheng
authors: C
authors: Xiang
authors: Department of Ultrasound Imaging, 306 Hospital of PLA, Beijing 100101, China.
authors: Huanyu
authors: H
authors: Zhou
authors: Institute of Immunology and Molecular Medicine, Jining Medical College, Jining 272067, China.|Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York 10029, NY, USA.
authors: Hui
authors: H
authors: Zhang
authors: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|Guangdong Provincial Key Laboratory of Gastroenterology, Guangzhou 510515, China.
authors: Qiang
authors: Q
authors: Zhang
authors: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|Guangdong Provincial Key Laboratory of Gastroenterology, Guangzhou 510515, China.
authors: Haitao
authors: H
authors: Qing
authors: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|Guangdong Provincial Key Laboratory of Gastroenterology, Guangzhou 510515, China.
authors: Bo
authors: B
authors: Jiang
authors: Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York 10029, NY, USA.
authors: Huabao
authors: H
authors: Xiong
authors: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|Guangdong Provincial Key Laboratory of Gastroenterology, Guangzhou 510515, China.|Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York 10029, NY, USA.
authors: Liang
authors: L
authors: Peng
mesh_terms: D000818:Animals; D051927:CD24 Antigen / Q000502:physiology*; D045744:Cell Line, Tumor; D002642:Chick Embryo; D015179:Colorectal Neoplasms / Q000098:blood supply*; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic / Q000209:etiology*; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology*
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; D018841:HSP90 Heat-Shock Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: CD24; Hsp90; VEGF; angiogenesis; colorectal cancer