EGFL6 promotes colorectal cancer cell growth and mobility and the anti‐cancer property of anti-EGFL6 antibody
Abstract Background The availability of a reliable tumor target for advanced colorectal cancer (CRC) therapeutic approaches is critical since current treatments are limited. Epidermal growth factor-like domain 6 (EGFL6) has been reported to be associated with cancer development. Here, we focused on...
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| Format: | Article |
| Language: | English |
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BMC
2021-03-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-021-00561-0 |
| _version_ | 1824026257190289408 |
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| author | Ting-Yi Sung Han-Li Huang Chun-Chun Cheng Fu-Ling Chang Po-Li Wei Ya-Wen Cheng Cheng-Chiao Huang Yu-Ching Lee Wei-Chun HuangFu Shiow-Lin Pan |
| author_facet | Ting-Yi Sung Han-Li Huang Chun-Chun Cheng Fu-Ling Chang Po-Li Wei Ya-Wen Cheng Cheng-Chiao Huang Yu-Ching Lee Wei-Chun HuangFu Shiow-Lin Pan |
| author_sort | Ting-Yi Sung |
| collection | DOAJ |
| description | Abstract Background The availability of a reliable tumor target for advanced colorectal cancer (CRC) therapeutic approaches is critical since current treatments are limited. Epidermal growth factor-like domain 6 (EGFL6) has been reported to be associated with cancer development. Here, we focused on the role of EGFL6 in CRC progression and its clinical relevance. In addition, an anti-EGFL6 antibody was generated by phage display technology to investigate its potential therapeutic efficacy in CRC. Results EGFL6 expression significantly increased in the colon tissues from CRC patients and mice showing spontaneous tumorigenesis, but not in normal tissue. Under hypoxic condition, EGFL6 expression was enhanced at both protein and transcript levels. Moreover, EGFL6 could promote cancer cell migration invasion, and proliferation of CRC cells via up-regulation of the ERK/ AKT pathway. EGFL6 also regulated cell migration, invasion, proliferation, and self-renewal through EGFR/αvβ3 integrin receptors. Treatment with the anti-EGFL6 antibody EGFL6-E5-IgG showed tumor-inhibition and anti-metastasis abilities in the xenograft and syngeneic mouse models, respectively. Moreover, EGFL6-E5-IgG treatment had no adverse effect on angiogenesis and wound healing Conclusions We demonstrated that EGFL6 plays a role in CRC tumorigenesis and tumor progression, indicating that EGFL6 is a potential therapeutic target worth further investigation. |
| first_indexed | 2024-12-19T11:12:05Z |
| format | Article |
| id | doaj.art-9bbf162c729e43c9b4a3fe7a24f4256f |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-12-19T11:12:05Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-9bbf162c729e43c9b4a3fe7a24f4256f2022-12-21T20:24:11ZengBMCCell & Bioscience2045-37012021-03-0111111410.1186/s13578-021-00561-0EGFL6 promotes colorectal cancer cell growth and mobility and the anti‐cancer property of anti-EGFL6 antibodyTing-Yi Sung0Han-Li Huang1Chun-Chun Cheng2Fu-Ling Chang3Po-Li Wei4Ya-Wen Cheng5Cheng-Chiao Huang6Yu-Ching Lee7Wei-Chun HuangFu8Shiow-Lin Pan9Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical UniversityPh.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical UniversityGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical UniversityGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical UniversityGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical UniversityPh.D. Program for Cancer Molecular Biology and Drug Discovery, Taipei Medical UniversityGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical UniversityPh.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical UniversityPh.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical UniversityPh.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical UniversityAbstract Background The availability of a reliable tumor target for advanced colorectal cancer (CRC) therapeutic approaches is critical since current treatments are limited. Epidermal growth factor-like domain 6 (EGFL6) has been reported to be associated with cancer development. Here, we focused on the role of EGFL6 in CRC progression and its clinical relevance. In addition, an anti-EGFL6 antibody was generated by phage display technology to investigate its potential therapeutic efficacy in CRC. Results EGFL6 expression significantly increased in the colon tissues from CRC patients and mice showing spontaneous tumorigenesis, but not in normal tissue. Under hypoxic condition, EGFL6 expression was enhanced at both protein and transcript levels. Moreover, EGFL6 could promote cancer cell migration invasion, and proliferation of CRC cells via up-regulation of the ERK/ AKT pathway. EGFL6 also regulated cell migration, invasion, proliferation, and self-renewal through EGFR/αvβ3 integrin receptors. Treatment with the anti-EGFL6 antibody EGFL6-E5-IgG showed tumor-inhibition and anti-metastasis abilities in the xenograft and syngeneic mouse models, respectively. Moreover, EGFL6-E5-IgG treatment had no adverse effect on angiogenesis and wound healing Conclusions We demonstrated that EGFL6 plays a role in CRC tumorigenesis and tumor progression, indicating that EGFL6 is a potential therapeutic target worth further investigation.https://doi.org/10.1186/s13578-021-00561-0EGFL6Colorectal cancerEGFR/αvβ3Tumor progressionTherapeutic antibody |
| spellingShingle | Ting-Yi Sung Han-Li Huang Chun-Chun Cheng Fu-Ling Chang Po-Li Wei Ya-Wen Cheng Cheng-Chiao Huang Yu-Ching Lee Wei-Chun HuangFu Shiow-Lin Pan EGFL6 promotes colorectal cancer cell growth and mobility and the anti‐cancer property of anti-EGFL6 antibody Cell & Bioscience EGFL6 Colorectal cancer EGFR/αvβ3 Tumor progression Therapeutic antibody |
| title | EGFL6 promotes colorectal cancer cell growth and mobility and the anti‐cancer property of anti-EGFL6 antibody |
| title_full | EGFL6 promotes colorectal cancer cell growth and mobility and the anti‐cancer property of anti-EGFL6 antibody |
| title_fullStr | EGFL6 promotes colorectal cancer cell growth and mobility and the anti‐cancer property of anti-EGFL6 antibody |
| title_full_unstemmed | EGFL6 promotes colorectal cancer cell growth and mobility and the anti‐cancer property of anti-EGFL6 antibody |
| title_short | EGFL6 promotes colorectal cancer cell growth and mobility and the anti‐cancer property of anti-EGFL6 antibody |
| title_sort | egfl6 promotes colorectal cancer cell growth and mobility and the anti cancer property of anti egfl6 antibody |
| topic | EGFL6 Colorectal cancer EGFR/αvβ3 Tumor progression Therapeutic antibody |
| url | https://doi.org/10.1186/s13578-021-00561-0 |
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