The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Cytokinesis Failure Triggers Hippo Tumor Suppressor Pathway Activation
Open accessAbstract
SUMMARY Genetically unstable tetraploid cells can promote tumorigenesis. Recent estimates suggest that ~37% of human tumors have undergone a genome-doubling event during their development. This potentially oncogenic effect of tetraploidy is countered by a p53-dependent barrier to proliferation. However, the cellular defects and corresponding signaling pathways that trigger growth suppression in tetraploid cells are not known. Here we combine RNAi screening and in vitro evolution approaches to demonstrate that cytokinesis failure activates the Hippo tumor suppressor pathway in cultured cells as well as in naturally occurring tetraploid cells in vivo. Induction of the Hippo pathway is triggered in part by extra centrosomes, which alter small G-protein signaling and activate LATS2 kinase. LATS2 in turn stabilizes p53 and inhibits the transcriptional regulators YAP and TAZ. These findings define an important tumor suppression mechanism and uncover adaptive mechanisms potentially available to nascent tumor cells that bypass this inhibitory regulation.
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Cites
Role of YAP/TAZ in mechanotransduction
Dupont, S., Morsut, L., Aragona, M., Enzo, E., Giulitti, S., Cordenonsi, M., Zanconato, F., Le Digabel, J., Forcato, M., Bicciato, S., et al. (2011) · Nature · doi:10.1038/nature10137 · Cited by 5,979
Cell Shape, Cytoskeletal Tension, and RhoA Regulate Stem Cell Lineage Commitment
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Elucidation of a universal size-control mechanism in Drosophila and mammals
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The Hippo Signaling Pathway in Development and Cancer
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Visualizing Spatiotemporal Dynamics of Multicellular Cell-Cycle Progression
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Self-citationPan-cancer patterns of somatic copy number alteration
Zack, T. I., Schumacher, S. E., Carter, S. L., Cherniack, A. D., Saksena, G., Tabak, B., Lawrence, M. S., Zhang, C.-Z., Wala, J., Mermel, C. H., et al. (2013) · Nature Genetics · doi:10.1038/ng.2760 · Cited by 1,870
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Regulation of the Hippo-YAP Pathway by G-Protein-Coupled Receptor Signaling
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A mechanism linking extra centrosomes to chromosomal instability
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Cited by
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Kastenhuber, E. R., & Lowe, S. W. (2017) · Cell · doi:10.1016/j.cell.2017.08.028 · Cited by 1,906
Mechanisms of Hippo pathway regulation
Meng, Z., Moroishi, T., & Guan, K.-L. (2016) · Genes & Development · doi:10.1101/gad.274027.115 · Cited by 1,667
The Hippo Pathway: Biology and Pathophysiology
Ma, S., Meng, Z., Chen, R., & Guan, K.-L. (2019) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-013118-111829 · Cited by 1,387
The Hippo Signaling Pathway in Development and Disease
Zheng, Y., & Pan, D. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.06.003 · Cited by 867
Metadata
- Authors
- Ganem, N. J., Cornils, H., Chiu, S.-Y., O’Rourke, K. P., Arnaud, J., Yimlamai, D., Théry, M., Camargo, F. D., & Pellman, D.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 158
- Issue
- 4
- Pages
- 833-848
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2149304739
- Cited by
- 373
- References
- 48
- FWCI
- 19.30
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ganem, N. J., Cornils, H., Chiu, S.-Y., O’Rourke, K. P., Arnaud, J., Yimlamai, D., Théry, M., Camargo, F. D., & Pellman, D. (2014). Cytokinesis Failure Triggers Hippo Tumor Suppressor Pathway Activation. Cell. https://doi.org/10.1016/j.cell.2014.06.029
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