Polycystic Kidney Disease (PKD)， which is attributable to mutations in the PKD1 and PKD2 genes encoding polycystin-1 (PC1) and polycystin-2 (PC2) respectively， shares common cellular defects with cancer， such as uncontrolled cell proliferation， abnormal differentiation and increased apoptosis. Interestingly， PC1 regulates many signalling pathways including Jak/STAT， mTOR， Wnt， AP-1 and calcineurin-NFAT which are also used by cancer cells for sending signals that will allow them to acquire and maintain malignant phenotypes. Nevertheless， the molecular relationship between polycystins and cancer is unknown. In this study， we investigated the role of PC1 in cancer biology using glioblastoma (GO... More
Polycystic Kidney Disease (PKD)， which is attributable to mutations in the PKD1 and PKD2 genes encoding polycystin-1 (PC1) and polycystin-2 (PC2) respectively， shares common cellular defects with cancer， such as uncontrolled cell proliferation， abnormal differentiation and increased apoptosis. Interestingly， PC1 regulates many signalling pathways including Jak/STAT， mTOR， Wnt， AP-1 and calcineurin-NFAT which are also used by cancer cells for sending signals that will allow them to acquire and maintain malignant phenotypes. Nevertheless， the molecular relationship between polycystins and cancer is unknown. In this study， we investigated the role of PC1 in cancer biology using glioblastoma (GOS3)， prostate (PC3)， breast (MCF7)， lung (A549) and colorectal (HT29) cancer cell lines. Our in vitro results propose that PC1 promotes cell migration in GOS3 cells and suppresses cell migration in A549 cells. In addition， PC1 enhances cell proliferation in GOS3 cells but inhibits it in MCF7， A549 and HT29 cells. We also found that PC1 up-regulates mTOR signalling and down-regulates Jak signalling in GOS3 cells， while it up-regulates mTOR signalling in PC3 and HT29 cells. Together， our study suggests that PC1 modulates cell proliferation and migration and interacts with mTOR and Jak signalling pathways in different cancer cell lines. Understanding the molecular details of how polycystins are associated with cancer may lead to the identification of new players in this devastating disease.
