Ting-Yi Sung1, Han-Li Huang1,2,3, Chun-Chun Cheng4, Fu-Ling Chang4, Po-Li Wei4,5,6,7, Ya-Wen Cheng8, Cheng-Chiao Huang9,10, Yu-Ching Lee11,12,13,14, Wei-Chun HuangFu15,16,17,18, Shiow-Lin Pan19,20,21,22,23. 1. Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, 11031, Taipei, Taiwan. 2. TMU Biomedical Commercialization Center, Taipei Medical University, 11031, Taipei, Taiwan. 3. TMU Research Center of Cancer Translational Medicine, Taipei Medical University, No. 250, Wuxing St., 11031, Taipei, Taiwan. 4. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, No. 250, Wuxing St., 11031, Taipei, Taiwan. 5. Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, 11031, Taipei, Taiwan. 6. Translational Laboratory, Department of Medical Research, Taipei Medical University Hospital, 11031, Taipei, Taiwan. 7. Department of Surgery, College of Medicine, Taipei Medical University, Taipei, Taiwan. 8. Ph.D. Program for Cancer Molecular Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan. 9. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, No. 250, Wuxing St., 11031, Taipei, Taiwan. GS4912@gmail.com. 10. Division of Breast Surgery, Department of Surgery, Taipei Medical University Hospital, No. 252, Wuxing St., 11031, Taipei, Taiwan. GS4912@gmail.com. 11. Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, 11031, Taipei, Taiwan. ycl@tmu.edu.tw. 12. TMU Biomedical Commercialization Center, Taipei Medical University, 11031, Taipei, Taiwan. ycl@tmu.edu.tw. 13. TMU Research Center of Cancer Translational Medicine, Taipei Medical University, No. 250, Wuxing St., 11031, Taipei, Taiwan. ycl@tmu.edu.tw. 14. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, No. 250, Wuxing St., 11031, Taipei, Taiwan. ycl@tmu.edu.tw. 15. Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, 11031, Taipei, Taiwan. clarehf@tmu.edu.tw. 16. TMU Research Center of Cancer Translational Medicine, Taipei Medical University, No. 250, Wuxing St., 11031, Taipei, Taiwan. clarehf@tmu.edu.tw. 17. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, No. 250, Wuxing St., 11031, Taipei, Taiwan. clarehf@tmu.edu.tw. 18. Ph.D. Program for Cancer Molecular Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan. clarehf@tmu.edu.tw. 19. Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, 11031, Taipei, Taiwan. slpan@tmu.edu.tw. 20. TMU Biomedical Commercialization Center, Taipei Medical University, 11031, Taipei, Taiwan. slpan@tmu.edu.tw. 21. TMU Research Center of Cancer Translational Medicine, Taipei Medical University, No. 250, Wuxing St., 11031, Taipei, Taiwan. slpan@tmu.edu.tw. 22. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, No. 250, Wuxing St., 11031, Taipei, Taiwan. slpan@tmu.edu.tw. 23. Ph.D. Program for Cancer Molecular Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan. slpan@tmu.edu.tw.
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.
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.
Authors: F Marmorino; D Rossini; S Lonardi; R Moretto; G Zucchelli; G Aprile; E Dell'Aquila; M Ratti; F Bergamo; G Masi; F Urbano; M Ronzoni; M Libertini; B Borelli; G Randon; A Buonadonna; G Allegrini; N Pella; V Ricci; A Boccaccino; T P Latiano; S Cordio; A Passardi; E Tamburini; L Boni; A Falcone; C Cremolini Journal: Ann Oncol Date: 2019-12-01 Impact factor: 32.976
Authors: Chad R Gordon; Yuri Rojavin; Mitul Patel; James E Zins; Generosa Grana; Brian Kann; Robert Simons; Umar Atabek Journal: Ann Plast Surg Date: 2009-06 Impact factor: 1.539