Polycystin-1 and polycystin-2 are involved in the acquisition of aggressive phenotypes in colorectal cancer.
The polycystins PC1 and PC2 are emerging as major players in mechanotransduction, a process that influences all steps of the invasion/metastasis cascade. We hypothesized that PC1 and PC2 facilitate cancer aggressiveness. Immunoblotting, RT-PCR, semi-quantitative and quantitative real-time PCR and FACS analyses were employed to investigate the effect of polycystin overexpression in colorectal cancer (CRC) cells. The impact of PC1 inhibition on cancer-cell proliferation was evaluated through an MTT assay. In vitro data were analyzed by Student's t-test. HT29 human xenografts were treated with anti-PC1 (extracellular domain) inhibitory antibody and analyzed via immunohistochemistry to determine the in vivo role of PC1 in CRC. Clinical significance was assessed by examining PC1 and PC2 protein expression in CRC patients (immunohistochemistry). In vivo and clinical data were analyzed by non-parametric tests, Kaplan-Meier curves, log-rank test and Cox model. All statistical tests were two-sided. PC1 overexpression promotes epithelial-to-mesenchymal transition (EMT) in HCT116 cells, while PC2 overexpression results in upregulation of the mTOR pathway in SW480 cells. PC1 inhibition causes reduced cell proliferation in CRC cells inducing tumor necrosis and suppressing EMT in HT29 tumor xenografts. In clinical study, PC1 and PC2 overexpression associates with adverse pathological parameters, including invasiveness and mucinous carcinomas. Moreover, PC1 overexpression appears as an independent prognostic factor of reduced recurrence-free survival (HR = 1.016, p = 0.03) and lowers overall survival probability, while aberrant PC2 expression predicts poor overall survival (p = 0.0468). These results support, for the first time, a direct link between mechanosensing polycystins (PC1 and PC2) and CRC progression.
['Gargalionis|Antonios N|AN|', 'Korkolopoulou|Penelope|P|', 'Farmaki|Elena|E|', 'Piperi|Christina|C|', 'Dalagiorgou|Georgia|G|', 'Adamopoulos|Christos|C|', 'Levidou|Georgia|G|', 'Saetta|Angelica|A|', 'Fragkou|Paraskevi|P|', 'Tsioli|Panagiota|P|', 'Kiaris|Hippokratis|H|', 'Zizi-Serbetzoglou|Adamantia|A|', 'Karavokyros|Ioannis|I|', 'Papavassiliou|Kostas A|KA|', 'Tsavaris|Nikolaos|N|', 'Patsouris|Efstratios|E|', 'Basdra|Efthimia K|EK|', 'Papavassiliou|Athanasios G|AG|']
D000368:Aged D000369:Aged, 80 and over D000818:Animals D045744:Cell Line, Tumor D049109:Cell Proliferation D015179:Colorectal Neoplasms D004195:Disease Models, Animal D018450:Disease Progression D058750:Epithelial-Mesenchymal Transition D005260:Female D015870:Gene Expression D064593:Heterografts D006801:Humans D007150:Immunohistochemistry D008207:Lymphatic Metastasis D008297:Male D051379:Mice D053842:Microsatellite Instability D008875:Middle Aged D060787:Neoplasm Grading D009367:Neoplasm Staging D010641:Phenotype D011379:Prognosis D015398:Signal Transduction D058570:TOR Serine-Threonine Kinases D050396:TRPP Cation Channels D047368:Tumor Burden
colorectal cancer polycystin invasion metastasis mechanosensor