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

Abstract

BackgroundA reliable cancer biomarker will be critical for advanced colorectal cancer (CRC) therapeutic approaches since current treatments are limited to certain patient characteristics, such as age, sex, comorbidities and patients received self-expandable metal stents implantations. The association of epidermal growth factor-like domain 6 (EGFL6) with cancer development has been reported. Here, we focused on the role of EGFL6 in CRC progression and its clinical relevance. An anti-EGFL6 antibody was generated by phage display technology to investigate the potential therapeutic efficacy in CRC. Student t test, Kruskal-Wallis test and multiple comparisons were used to statistical analysis results.ResultsSignificant EGFL6 expression was found in colon tissues from patients and spontaneous tumorigenesis mouse but not in normal tissue. Under hypoxia condition, EGFL6 expression were enhanced in protein and transcript-level. Furthermore, we found EGFL6 could enhance cancer cell migration, invasion and proliferation in CRC via up-regulating ERK/ AKT pathway, as well as reducing ADAMTS1 and Snail expression. We also found EGFL6 regulates cell abilities through EGFR/αvβ3 integrin receptors. By conducting animal experiments, our anti-EGFL6 antibody, EGFL6-E5-IgG, showed tumor inhibition and anti-metastasis ability. Furthermore, no impact on angiogenesis and wound healing by using EGFL6-E5-IgG were observed.ConclusionsWe demonstrated that EGFL6 plays a role in CRC tumorigenesis and tumor progression, indicating that EGFL6 is a potential cancer biomarker and therapeutic target worth further investigation.