Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM
Abstract 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 In...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-02-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-03906-0 |
| _version_ | 1811171567948791808 |
|---|---|
| author | Weijun Wang Xuelian Tang Caihan Duan Shuxin Tian Chaoqun Han Wei Qian Xin Jiang Xiaohua Hou Rong Lin |
| author_facet | Weijun Wang Xuelian Tang Caihan Duan Shuxin Tian Chaoqun Han Wei Qian Xin Jiang Xiaohua Hou Rong Lin |
| author_sort | Weijun Wang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-10T17:16:10Z |
| format | Article |
| id | doaj.art-6bf133c3469c40f4804bd75f773587b9 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-10T17:16:10Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-6bf133c3469c40f4804bd75f773587b92023-02-05T12:22:33ZengBMCJournal of Translational Medicine1479-58762023-02-0121111410.1186/s12967-023-03906-0Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAMWeijun Wang0Xuelian Tang1Caihan Duan2Shuxin Tian3Chaoqun Han4Wei Qian5Xin Jiang6Xiaohua Hou7Rong Lin8Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract 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.https://doi.org/10.1186/s12967-023-03906-0Fut2MCAMFucosylationColorectal cancerCRC |
| spellingShingle | Weijun Wang Xuelian Tang Caihan Duan Shuxin Tian Chaoqun Han Wei Qian Xin Jiang Xiaohua Hou Rong Lin Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM Journal of Translational Medicine Fut2 MCAM Fucosylation Colorectal cancer CRC |
| title | Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM |
| title_full | Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM |
| title_fullStr | Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM |
| title_full_unstemmed | Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM |
| title_short | Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM |
| title_sort | intestinal epithelium specific fut2 deficiency promotes colorectal cancer through down regulating fucosylation of mcam |
| topic | Fut2 MCAM Fucosylation Colorectal cancer CRC |
| url | https://doi.org/10.1186/s12967-023-03906-0 |
| work_keys_str_mv | AT weijunwang intestinalepitheliumspecificfut2deficiencypromotescolorectalcancerthroughdownregulatingfucosylationofmcam AT xueliantang intestinalepitheliumspecificfut2deficiencypromotescolorectalcancerthroughdownregulatingfucosylationofmcam AT caihanduan intestinalepitheliumspecificfut2deficiencypromotescolorectalcancerthroughdownregulatingfucosylationofmcam AT shuxintian intestinalepitheliumspecificfut2deficiencypromotescolorectalcancerthroughdownregulatingfucosylationofmcam AT chaoqunhan intestinalepitheliumspecificfut2deficiencypromotescolorectalcancerthroughdownregulatingfucosylationofmcam AT weiqian intestinalepitheliumspecificfut2deficiencypromotescolorectalcancerthroughdownregulatingfucosylationofmcam AT xinjiang intestinalepitheliumspecificfut2deficiencypromotescolorectalcancerthroughdownregulatingfucosylationofmcam AT xiaohuahou intestinalepitheliumspecificfut2deficiencypromotescolorectalcancerthroughdownregulatingfucosylationofmcam AT ronglin intestinalepitheliumspecificfut2deficiencypromotescolorectalcancerthroughdownregulatingfucosylationofmcam |