VEGF-A/Neuropilin 1 Pathway Confers Cancer Stemness via Activating Wnt/β-Catenin Axis in Breast Cancer Cells

Background/aims: Targeting Cancer Stem Cells (CSCs) is emerging as a promising method for Cancer treatment. We previously indicated that knockdown of Neuropilin 1(NRP-1) could inhibit breast Cancer cell proliferation. Here, we continue exploring the roles and mechanisms of VEGF-A/NRP-1 axis in breast CSCs formation.

Methods: qRT-PCR was used to detect the levels of VEGF-A and NRP-1 in breast Cancer sphere cells and wild-type cells. Mammospheres formation, flow cytometry, soft agar colony and tumor formation assays were performed to evaluate the effects of VEGF-A/NRP-1 on breast Cancer stemness. Further HUVECs tube formation, cell invasion assays were carried out to detect the effects of VEGF-A/NRP-1 on breast Cancer spheres-induced angiogenesis. Finally, Annexin V/PI Apoptosis and CCK8 assays were used to detect the effects of VEGF-A/NRP-1 on chemoresistance.

Results: Overexpression of VEGF-A or NRP-1 conferred CSCs-related traits in MCF-7 cells, while knockdown of VEGF-A or NRP-1 reduced CSCs-related traits in MDA-MB-231 cells in vitro and in vivo. Notably, VEGF-A acted in a NRP-1 dependent way. Mechanistically, the VEGF-A/NRP-1 axis conferred CSCs phenotype via activating Wnt/β-catenin pathway.

Conclusion: our results suggest that VEGF-A/NRP-1 axis could confer CSCs-related traits and chemoresistance.