Angiopoietin-like 3 (ANGPTL3) drives cell proliferation, migration and angiogenesis in cervical cancer via binding to integrin alpha v beta 3

Angiopoietin-like 3 (ANGPTL3) has been uncovered to play an oncogenic role in several kinds of human malignancies. Nevertheless, whether ANGPTL3 functions in cervical cancer (CC) has not yet been reported. This paper is intended to explore the impact of ANGPTL3 on CC cells and elucidate the potential mechanism. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to analyze the ANGPTL3 expression. Western blot was also performed to examine integrin alpha v beta 3 protein level. Cell proliferation was evaluated by MTT assay, EdU staining and Western blot analysis. In addition, the migratory and invasive abilities of cells were, respectively, estimated by wound healing and transwell assays. Tube formation assay was performed to determine endothelial cell angiogenesis. Levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) were measured by ELISA. As a result, ANGPTL3 expression was significantly higher in CC cells relative to that in normal cervical cells. Silencing of ANGPTL3 suppressed cell proliferation, migration and invasion. Besides, downregulation of ANGPTL3 inhibited human umbilical vein endothelial cell (HUVEC) angiogenesis and repressed protein level of integrin alpha v beta 3 (alpha v beta 3). Upregulation of alpha v beta 3 offsets the inhibitory effect of ANGPTL3 on proliferation, migration and invasion in CC cells. Upregulated expression of alpha v beta 3 promoted blood vessel formation and secretions of VEGF and VEGFR2. In conclusion, ANGPTL3 silencing may serve as a tumor suppressor in CC through integrin alpha v beta 3, which provides a potentially novel therapeutic target for patients with CC.

Automated summary

It has been discovered that ANGPTL3 plays an oncogenic role in several types of human malignancies. This study found that ANGPTL3 is highly expressed in cervical cancer cells and silencing ANGPTL3 can inhibit cell proliferation, migration, invasion, and angiogenesis. The inhibitory effect of ANGPTL3 can be offset by upregulating the expression of alpha v beta 3, which also promotes blood vessel formation and the secretion of VEGF and VEGFR2 in cervical cancer cells.