EGFL7 as a novel therapeutic candidate regulates cell invasion and anoikis in colorectal cancer through PI3K/AKT signaling pathway.

backgroundAnoikis is a form of apoptosis, which inhibits metastatic cascade and deprives cancer cells with invasive capacity. Epidermal growth factor-like domain-containing protein 7 (EGFL7) is overexpressed in colorectal cancer (CRC) and is a potential biomarker for malignancy. The present study aimed was to investigate the effect and underlying mechanism of EGFL7 on CRC cell function.

methodsEGFL7 expression in mutable human CRC cell lines and normal intestinal epithelial cell line HIEC were measured by qRT-PCR. To investigate the biological functions of EGFL7, loss-of-function experiments were performed by transfecting EGFL7 siRNA into SW620 and LoVo cells. Western blot analysis, MTT, invasion and anoikis assay were used to explore the underlying mechanism of EGFL7.

resultsEGFL7 was upregulated in several CRC cell lines as compared with normal intestinal epithelial cell line HIEC. Transfection of EGFL7 siRNA significantly decreased cell proliferation and invasion capacity of SW620 and LoVo cells. Additionally, EGFL7 inhibition markedly elevated anoikis through modulating anoikis marker proteins as reflected by increasing of cleaved-caspase-3 and cleaved-PAPR expression. Moreover, downregulation of EGFL7 inhibited PI3K and P-AKT expression. Furthermore, re-expression of PI3K remarkably reversed the effects of EGFL7 on SW620 cells.

conclusionOverall, our findings suggested that EGFL7 acts as an oncogene, regulated CRC invasion and anoikis through PI3K/AKT signaling, which provided a theoretical basis for EGFL7 as a potential therapeutic target of CRC treatment.