Pocaterra, Arianna and Scattolin, Gloria and Romani, Patrizia and Ament, Cindy and Ribback, Silvia and Chen, Xin and Evert, Matthias and Calvisi, Diego F. and Dupont, Sirio (2021) Fascin1 empowers YAP mechanotransduction and promotes cholangiocarcinoma development. COMMUNICATIONS BIOLOGY, 4 (1): 763. ISSN , 2399-3642
Full text not available from this repository. (Request a copy)Abstract
Pocaterra et al. demonstrate that Fascin1 F-actin bundling protein sustains YAP activation in the tumour environment in response to extracellular matrix mechanical cues. This study highlights Fascin1 as a potential clinical target in intrahepatic cholangiocarcinoma development. Mechanical forces control cell behavior, including cancer progression. Cells sense forces through actomyosin to activate YAP. However, the regulators of F-actin dynamics playing relevant roles during mechanostransduction in vitro and in vivo remain poorly characterized. Here we identify the Fascin1 F-actin bundling protein as a factor that sustains YAP activation in response to ECM mechanical cues. This is conserved in the mouse liver, where Fascin1 regulates YAP-dependent phenotypes, and in human cholangiocarcinoma cell lines. Moreover, this is relevant for liver tumorigenesis, because Fascin1 is required in the AKT/NICD cholangiocarcinogenesis model and it is sufficient, together with AKT, to induce cholangiocellular lesions in mice, recapitulating genetic YAP requirements. In support of these findings, Fascin1 expression in human intrahepatic cholangiocarcinomas strongly correlates with poor patient prognosis. We propose that Fascin1 represents a pro-oncogenic mechanism that can be exploited during intrahepatic cholangiocarcinoma development to overcome a mechanical tumor-suppressive environment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIPPO PATHWAY; F-ACTIN; CAPPING PROTEIN; CONTACT INHIBITION; TISSUE-GROWTH; LIVER-CANCER; ORGAN SIZE; CELL; YAP/TAZ; MOUSE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Sep 2022 13:46 |
| Last Modified: | 13 Sep 2022 13:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47356 |
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