Your browser doesn't support javascript.
loading
Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM.
Wang, Weijun; Tang, Xuelian; Duan, Caihan; Tian, Shuxin; Han, Chaoqun; Qian, Wei; Jiang, Xin; Hou, Xiaohua; Lin, Rong.
Afiliación
  • Wang W; Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Tang X; Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Duan C; Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Tian S; Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Han C; Department of Gastroenterology, The First Affiliated Hospital of Medical College, Shihezi University, Shihezi, 832008, China.
  • Qian W; Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Jiang X; Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Hou X; Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Lin R; Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. houxh@hust.edu.cn.
J Transl Med ; 21(1): 82, 2023 02 04.
Article en En | MEDLINE | ID: mdl-36739428
BACKGROUND: Our previous study showed that fucosyltransferase 2 (Fut2) deficiency is closely related to colitis. Colitis increases the risk for the development of colorectal cancer (CRC). This study aimed to investigate the effect and underlying mechanism of action of Fut2 in CRC. METHODS: Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice were used in this study. CRC was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Immunofluorescence was used to examine the fucosylation levels. Proteomics and N-glycoproteomics analyses, Ulex Europaeus Agglutinin I (UEA-I) affinity chromatography, immunoprecipitation, and rescue assay were used to investigate the mechanism of Fut2 in CRC. RESULTS: The expression of Fut2 and α-1,2-fucosylation was lower in colorectal tumor tissues than in the adjacent normal tissues of AOM/DSS-induced CRC mice. More colorectal tumors were detected in Fut2△IEC mice than in control mice, and significant downregulation of melanoma cell adhesion molecule (MCAM) fucosylation was detected in the colorectal tumor tissues of Fut2△IEC mice. Overexpression of Fut2 inhibited cell proliferation, invasion and tumor metastasis in vivo and in vitro in SW480 and HCT116 cells. Moreover, fucosylation of MCAM may be a mediator of Fut2 in CRC. Peracetylated 2-F-Fuc, a fucosyltransferase inhibitor, repressed fucosylation modification of MCAM and reversed the inhibitory effects of Fut2 overexpression on SW480 cell proliferation, migration, and invasion. Our results indicate that Fut2 deficiency in the intestinal epithelium promotes CRC by downregulating the fucosylation of MCAM. CONCLUSIONS: The regulation of fucosylation may be an potential therapy for CRC, especially in patients with Fut2 gene defects.
Asunto(s)
Palabras clave

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Colitis Límite: Animals Idioma: En Revista: J Transl Med Año: 2023 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Colitis Límite: Animals Idioma: En Revista: J Transl Med Año: 2023 Tipo del documento: Article País de afiliación: China