Brachyury promotes proliferation and migration of colorectal cancer cells by targeting MMP14
Abstract Background The incidence and mortality rates of colorectal cancer (CRC) are rising, and it is the second most common cause of cancer-related deaths worldwide. Although the transcription factor, Brachyury is intricately linked with various clinical malignancies, the mechanisms by which it in...
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BMC
2025-04-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03726-w |
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| author | Ming Chen Huiheng Qu Xiao Liang Ying Huang Zhengjie Yang Pei Lu Keqin Shi Peng Chen Yanjing Zhang Hui Zhou Jiazeng Xia Jun Shen |
| author_facet | Ming Chen Huiheng Qu Xiao Liang Ying Huang Zhengjie Yang Pei Lu Keqin Shi Peng Chen Yanjing Zhang Hui Zhou Jiazeng Xia Jun Shen |
| author_sort | Ming Chen |
| collection | DOAJ |
| description | Abstract Background The incidence and mortality rates of colorectal cancer (CRC) are rising, and it is the second most common cause of cancer-related deaths worldwide. Although the transcription factor, Brachyury is intricately linked with various clinical malignancies, the mechanisms by which it influences CRC cell proliferation and migration are inadequately understood. Methods Tissue microarray was used to evaluate Brachyury expression in CRC and adjacent normal tissues. The effects of Brachyury on HCT116 and SW480 CRC cells were also examined in vitro, including using Cell Counting Kit-8, colony formation, and transwell assays, and in vivo through subcutaneous tumorigenesis assays in a nude mouse xenograft model. Chromatin immunoprecipitation was used to evaluate Brachyury binding to the MMP14 promoter and its impact on MMP14 expression. Rescue experiments were used to elucidate MMP14’s role in mediating Brachyury’s effect on CRC cell behavior. Results Brachyury expression was significantly higher in CRC tissues than in adjacent normal tissues, and it promotes CRC oncogenesis in vitro and in vivo. Rescue experiments established MMP14 as a direct, downstream Brachyury target, affirming that MMP14 enhanced Brachyury-driven CRC cell proliferation. Conclusion Our findings highlight targeting the Brachyury–MMP14 axis as a potential novel approach for CRC clinical therapy. |
| format | Article |
| id | doaj-art-a904a86c8d064616bdecd8a62b7dd660 |
| institution | OA Journals |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-a904a86c8d064616bdecd8a62b7dd6602025-08-20T02:11:47ZengBMCCancer Cell International1475-28672025-04-0125111410.1186/s12935-025-03726-wBrachyury promotes proliferation and migration of colorectal cancer cells by targeting MMP14Ming Chen0Huiheng Qu1Xiao Liang2Ying Huang3Zhengjie Yang4Pei Lu5Keqin Shi6Peng Chen7Yanjing Zhang8Hui Zhou9Jiazeng Xia10Jun Shen11Department of Orthopeadic Surgery, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical UniversityDepartment of General Surgery, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical UniversityDepartment of Anesthesiology, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical UniversityDepartment of Ultrasonography, The Fifth People’s Hospital of SuzhouDepartment of Orthopeadic Surgery, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical UniversityDepartment of Orthopeadic Surgery, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical UniversityDepartment of Orthopeadic Surgery, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical UniversityDepartment of Orthopeadic Surgery, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical UniversityDepartment of Orthopeadic Surgery, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical UniversityHuman Reproductive and Genetic Center, Affiliated Hospital of Jiangnan UniversityDepartment of General Surgery, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical UniversityDepartment of Orthopeadic Surgery, Suzhou Municipal Hospital, the Affiliated Suzhou Hospital of Nanjing Medical UniversityAbstract Background The incidence and mortality rates of colorectal cancer (CRC) are rising, and it is the second most common cause of cancer-related deaths worldwide. Although the transcription factor, Brachyury is intricately linked with various clinical malignancies, the mechanisms by which it influences CRC cell proliferation and migration are inadequately understood. Methods Tissue microarray was used to evaluate Brachyury expression in CRC and adjacent normal tissues. The effects of Brachyury on HCT116 and SW480 CRC cells were also examined in vitro, including using Cell Counting Kit-8, colony formation, and transwell assays, and in vivo through subcutaneous tumorigenesis assays in a nude mouse xenograft model. Chromatin immunoprecipitation was used to evaluate Brachyury binding to the MMP14 promoter and its impact on MMP14 expression. Rescue experiments were used to elucidate MMP14’s role in mediating Brachyury’s effect on CRC cell behavior. Results Brachyury expression was significantly higher in CRC tissues than in adjacent normal tissues, and it promotes CRC oncogenesis in vitro and in vivo. Rescue experiments established MMP14 as a direct, downstream Brachyury target, affirming that MMP14 enhanced Brachyury-driven CRC cell proliferation. Conclusion Our findings highlight targeting the Brachyury–MMP14 axis as a potential novel approach for CRC clinical therapy.https://doi.org/10.1186/s12935-025-03726-wBrachyuryColorectal cancerMMP14ProliferationMigration |
| spellingShingle | Ming Chen Huiheng Qu Xiao Liang Ying Huang Zhengjie Yang Pei Lu Keqin Shi Peng Chen Yanjing Zhang Hui Zhou Jiazeng Xia Jun Shen Brachyury promotes proliferation and migration of colorectal cancer cells by targeting MMP14 Cancer Cell International Brachyury Colorectal cancer MMP14 Proliferation Migration |
| title | Brachyury promotes proliferation and migration of colorectal cancer cells by targeting MMP14 |
| title_full | Brachyury promotes proliferation and migration of colorectal cancer cells by targeting MMP14 |
| title_fullStr | Brachyury promotes proliferation and migration of colorectal cancer cells by targeting MMP14 |
| title_full_unstemmed | Brachyury promotes proliferation and migration of colorectal cancer cells by targeting MMP14 |
| title_short | Brachyury promotes proliferation and migration of colorectal cancer cells by targeting MMP14 |
| title_sort | brachyury promotes proliferation and migration of colorectal cancer cells by targeting mmp14 |
| topic | Brachyury Colorectal cancer MMP14 Proliferation Migration |
| url | https://doi.org/10.1186/s12935-025-03726-w |
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