EGFL6 promotes colorectal cancer cell growth and mobility and the anti‐cancer property of anti-EGFL6 antibody

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 expressionsignificantly increased in the colon tissues from CRC patients and mice showingspontaneous tumorigenesis, but not in normal tissue. Under hypoxic condition, EGFL6expression was enhanced at both protein and transcript levels. Moreover, EGFL6could promote cancer cell migration invasion, and proliferation of CRC cells via up-regulation ofthe ERK/ AKT pathway. EGFL6 also regulated cell migration, invasion,proliferation, and self-renewal through EGFR/αvβ3 integrin receptors. Treatmentwith the anti-EGFL6 antibody EGFL6-E5-IgG showed tumor-inhibition andanti-metastasis abilities in the xenograft and syngeneic mouse models,respectively. Moreover, EGFL6-E5-IgG treatment had no adverse effect onangiogenesis 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.