Selenium binding protein 1 inhibits tumor angiogenesis in colorectal cancers by blocking the Delta-like ligand 4/Notch1 signaling pathway
Background: Selenium binding protein 1 (SELENBP1) is frequently downregulated in malignancies such as colorectal cancer (CRC), however, whether it is involved in tumor angiogenesis is still unknown. Methods: We analyzed the expression and localization of SELENBP1 in vessels from CRC and neighboring...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523322000274 |
| _version_ | 1818329812483178496 |
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| author | Xiaotian Zhang Runqi Hong Lanxin Bei Ju Yang Xiaomei Zhao Zhiqing Hu Liang Chen He Meng Qian Zhang Gengming Niu Ying Yue Chongwei Ke |
| author_facet | Xiaotian Zhang Runqi Hong Lanxin Bei Ju Yang Xiaomei Zhao Zhiqing Hu Liang Chen He Meng Qian Zhang Gengming Niu Ying Yue Chongwei Ke |
| author_sort | Xiaotian Zhang |
| collection | DOAJ |
| description | Background: Selenium binding protein 1 (SELENBP1) is frequently downregulated in malignancies such as colorectal cancer (CRC), however, whether it is involved in tumor angiogenesis is still unknown. Methods: We analyzed the expression and localization of SELENBP1 in vessels from CRC and neighboring tissues. We investigated the in vitro and in vivo activity of SELENBP1 in angiogenesis and explored the underlying mechanism. Results: SELENBP1 was localized to endothelial cells in addition to glandular cells, while its vascular expression was decreased in tumor vessels compared to that in vessels from neighboring non-tumor tissues. Gain-of-function and loss-of-function experiments demonstrated that SELENBP1 inhibited angiogenesis in vitro, and blocked communications between HUVECs and CRC cells. Overexpression of SELENBP1 in CRC cells inhibited tumor growth and angiogenesis, and enhanced bevacizumab-sensitivity in a mouse subcutaneous xenograft model. Mechanic analyses revealed that SELENBP1 may suppress tumor angiogenesis by binding with Delta-like ligand 4 (DLL4) and antagonizing the DLL4/Notch1 signaling pathway. The inhibitory effects of SELENBP1 on in vitro angiogenesis could largely be rescued by DLL4. Conclusion: These results revealed a novel role of SELENBP1 as a potential tumor suppressor that antagonizes tumor angiogenesis in CRC by intervening the DLL4/Notch1 signaling pathway. |
| first_indexed | 2024-12-13T12:54:00Z |
| format | Article |
| id | doaj.art-45350e3a876c441a9d6d7122f13417d3 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-13T12:54:00Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-45350e3a876c441a9d6d7122f13417d32022-12-21T23:45:15ZengElsevierTranslational Oncology1936-52332022-04-0118101365Selenium binding protein 1 inhibits tumor angiogenesis in colorectal cancers by blocking the Delta-like ligand 4/Notch1 signaling pathwayXiaotian Zhang0Runqi Hong1Lanxin Bei2Ju Yang3Xiaomei Zhao4Zhiqing Hu5Liang Chen6He Meng7Qian Zhang8Gengming Niu9Ying Yue10Chongwei Ke11Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, ChinaDepartment of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, ChinaDepartment of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, ChinaDepartment of Pathology, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, ChinaDepartment of Medicine, Dongying New District Hospital, Dongying, Shandong 257000, ChinaDepartment of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, ChinaDepartment of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, ChinaDepartment of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, ChinaDepartment of Orthopedics, The Affiliated Huaihai Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221300, ChinaDepartment of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, China; Corresponding authors.Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, China; Corresponding authors.Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, China; Corresponding authors.Background: Selenium binding protein 1 (SELENBP1) is frequently downregulated in malignancies such as colorectal cancer (CRC), however, whether it is involved in tumor angiogenesis is still unknown. Methods: We analyzed the expression and localization of SELENBP1 in vessels from CRC and neighboring tissues. We investigated the in vitro and in vivo activity of SELENBP1 in angiogenesis and explored the underlying mechanism. Results: SELENBP1 was localized to endothelial cells in addition to glandular cells, while its vascular expression was decreased in tumor vessels compared to that in vessels from neighboring non-tumor tissues. Gain-of-function and loss-of-function experiments demonstrated that SELENBP1 inhibited angiogenesis in vitro, and blocked communications between HUVECs and CRC cells. Overexpression of SELENBP1 in CRC cells inhibited tumor growth and angiogenesis, and enhanced bevacizumab-sensitivity in a mouse subcutaneous xenograft model. Mechanic analyses revealed that SELENBP1 may suppress tumor angiogenesis by binding with Delta-like ligand 4 (DLL4) and antagonizing the DLL4/Notch1 signaling pathway. The inhibitory effects of SELENBP1 on in vitro angiogenesis could largely be rescued by DLL4. Conclusion: These results revealed a novel role of SELENBP1 as a potential tumor suppressor that antagonizes tumor angiogenesis in CRC by intervening the DLL4/Notch1 signaling pathway.http://www.sciencedirect.com/science/article/pii/S1936523322000274Selenium binding proteinColorectal cancerAngiogenesisDelta-like ligand 4Notch signaling pathway |
| spellingShingle | Xiaotian Zhang Runqi Hong Lanxin Bei Ju Yang Xiaomei Zhao Zhiqing Hu Liang Chen He Meng Qian Zhang Gengming Niu Ying Yue Chongwei Ke Selenium binding protein 1 inhibits tumor angiogenesis in colorectal cancers by blocking the Delta-like ligand 4/Notch1 signaling pathway Translational Oncology Selenium binding protein Colorectal cancer Angiogenesis Delta-like ligand 4 Notch signaling pathway |
| title | Selenium binding protein 1 inhibits tumor angiogenesis in colorectal cancers by blocking the Delta-like ligand 4/Notch1 signaling pathway |
| title_full | Selenium binding protein 1 inhibits tumor angiogenesis in colorectal cancers by blocking the Delta-like ligand 4/Notch1 signaling pathway |
| title_fullStr | Selenium binding protein 1 inhibits tumor angiogenesis in colorectal cancers by blocking the Delta-like ligand 4/Notch1 signaling pathway |
| title_full_unstemmed | Selenium binding protein 1 inhibits tumor angiogenesis in colorectal cancers by blocking the Delta-like ligand 4/Notch1 signaling pathway |
| title_short | Selenium binding protein 1 inhibits tumor angiogenesis in colorectal cancers by blocking the Delta-like ligand 4/Notch1 signaling pathway |
| title_sort | selenium binding protein 1 inhibits tumor angiogenesis in colorectal cancers by blocking the delta like ligand 4 notch1 signaling pathway |
| topic | Selenium binding protein Colorectal cancer Angiogenesis Delta-like ligand 4 Notch signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S1936523322000274 |
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