Loss of neuropilin 1 inhibits liver cancer stem cells population and blocks metastasis in hepatocellular carcinoma via epithelial-mesenchymal transition

It is generally believed that the existence of cancer stem cells (CSCs) is related to tumor recurrence and metastasis of hepatocellular carcinoma (HCC). Neuropilin 1 (NRP1) is involved in numerous pathophysiological processes of tumor progression, however, whether NRP1 is involved in the regulation of liver CSCs and metastasis of HCC is still unknown. In the present study, we examined the effect of NRP1 on the population of liver CSCs and the metastasis mechanism of HCC. In NRP1 small hairpin RNA (shRNA)-transduced HCC cells, liver CSCs surface markers (CD133+/EpCAM+/CD13+/CD44+) expressing cells, which imply the CSCs population, were decreased. Transwell assay and nude mouse liver orthotopic transplantation model confirmed that NRP1 knockdown inhibited HCC cells' migration and lung metastasis. Our data showed that the expression of NRP1 was upregulated in 5 independent cohorts of HCC patients, consequently, high levels of NRP1 correlated with recurrence and poor prognosis in HCC. Mechanism research showed that NRP1 promotes cell spreading through the epithelial-mesenchymal transition (EMT) signaling pathway. In summary, NRP1 enhanced the population of liver CSCs and migration of HCC via EMT, indicating that NRP1 might be a novel target for HCC treatments.