| Neuropilin (Nrp) overexpression is correlated with increased invasion and metastasis in many epithelial carcinomas including breast cancer. The exact molecular mechanism of how Nrp promotes cancer cell tumourigenicity is unknown. Nrp is a coreceptor for VEGF, hepatocyte growth factor (HGF), and also shown to activate TGF-beta on tumour cells. We hypothesize that binding of Nrp potentiates growth factor (GF) signalling and results in GF-dependent aggressive phenotype in breast cancer. In the current study, Nrp was shown to potentiate HGF signalling in vitro in MCF-7 cells by increasing phosphorylation of the MET receptor. However MDA-MB-231 cell line failed to show any differences after Nrp knockdown, due to constitutively activated MET. Nrp is also shown to increase the number and size of cancer stem cell (CSC) enriched mammospheres through NF-kappaB pathway activation. These results suggest a novel function of Nrp in CSCs and identify it as a potential target for effective cancer therapy. |
