What question did this study set out to answer?

The study aims to define the roles of polycystin-1 and polycystin-2 in tumor biology, particularly focusing on mechanotransduction and EMT processes in solid tumors.

April 7, 2026International Journal of Biological Sciences0 citationsOpen Access

Polycystin-1 Orchestrates Tumor Context-Dependent Mechanotransduction Programs Driving Epithelial-to-Mesenchymal Transition and Invasion in Solid Cancers

AGAntonios N. GargalionisNational and Kapodistrian University of Athens KPKostas A. Papavassiliou AGAngeliki-Ioanna GiannopoulouNational and Kapodistrian University of Athens

Key Points

The study aims to define the roles of polycystin-1 and polycystin-2 in tumor biology, particularly focusing on mechanotransduction and EMT processes in solid tumors.
Analyzed PC1 and PC2 expression in human lung, breast, prostate, and brain tumors.
Utilized xenograft models to modulate PC1 function with a blocking antibody.
Employed PKD1 siRNA in cancer cell lines to assess effects on EMT and migration.
Measured correlations with clinicopathological features and survival outcomes.
PC1 and PC2 showed strong positive correlation across diverse tumor types.
High PC1 and PC2 levels were associated with aggressive cancer features, such as PD-L1 expression and worse survival in HER2 breast cancer.
Inhibition of PC1 mechanosensing reduced EMT and tumor growth across tumor types.
PKD1 silencing lowered cell migration and modified EMT marker expression context-dependently.

Abstract

Mechanotransduction critically shapes tumor progression by regulating cytoskeletal remodeling, epithelial-to-mesenchymal transition (EMT), invasion, and immune evasion.Polycystin-1 (PC1) and polycystin-2 (PC2), established mechanosensitive proteins in epithelial systems, have recently been implicated in tumor biology; however, their roles across diverse solid malignancies remain insufficiently defined.We assessed PC1 and PC2 expression patterns and their associations with clinicopathological features in human lung, breast, prostate, and brain tumors.PC1 functional modulation was performed in xenograft models using an extracellular mechanosensitivity-blocking antibody, and in cancer cell lines via polycystic kidney disease 1 (PKD1) siRNA.We evaluated consequences on EMT, tumor growth, migration, and the mechanotransduction effector TAZ.PC1 and PC2 exhibited strong positive correlation across multiple tumor types, indicating coordinated mechanobiological regulation in cancer.Their expression associated with clinically aggressive features, including PD-L1 expression in lung cancer, adverse pathological characteristics in prostate cancer, and poorer survival in HER2 breast cancer with elevated PC2 levels.In vivo, inhibition of PC1 mechanosensing consistently attenuated EMT programs across tumor types, accompanied by reductions in tumor growth.In vitro, PKD1 silencing reduced cell migration and induced context-dependent modulation of EMT markers.Notably, PC1 suppression induced TAZ activation in breast cancer and glioma cells, indicating a cell type-specific regulatory interaction between PC1 and Hippo-mechanotransduction signaling.Our data suggest that polycystins, PC1 in particular, exert conserved yet context-dependent mechanoregulatory functions in solid tumors.By influencing EMT, migration, tumor progression, and TAZ-mediated mechanotransduction, PC1 emerges as a potential biomarker and mechanotherapeutic target in mechanically responsive cancers.

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