Polycystin-1 induces activation of the PI3K/AKT/mTOR pathway and promotes angiogenesis in renal cell carcinoma.

In the present study we investigated the expression and the functional role of mechanosensitive polycystins in renal cell carcinoma (RCC). In 115 RCC patients we evaluated the protein expression of polycystin-1 (PC1), polycystin-2 (PC2), VEGF and protein components of the PI3K/Akt/mTOR pathway, which have been implicated both in RCC and polycystic kidney disease. PC1 and PC2 demonstrated reduced expression throughout the RCC tissue compared to the adjacent normal tissue. PC1 and PC2 revealed high expression when they were associated with higher grade and decreased 5-year survival respectively. PC1 and PC2 were positively correlated with p110γ subunit of PI3K and high PC1 expressing cells tended to display activation/phosphorylation of Akt. There was also a positive association between PC1 and VEGF expression, whereas PC1 augmented the tumor's microvascular network in stage IV carcinomas. In human RCC cells, functional inhibition of PC1 resulted in upregulation of the PI3K/Akt/mTOR pathway, enhanced cell proliferation and led to inhibition of cell migration. Conclusively, aberrant PC1 regulation is associated with increased angiogenesis and features of advanced disease in RCC tissues.