Down-regulation of LATS kinases alters p53 to promote cell migration
- Noa Furth1,5,
- Noa Bossel Ben-Moshe2,5,
- Yair Pozniak3,
- Ziv Porat4,
- Tamar Geiger3,
- Eytan Domany2,
- Yael Aylon1 and
- Moshe Oren1
- 1Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel;
- 2Department of Physics of Complex Systems, The Weizmann Institute of Science, Rehovot 76100, Israel;
- 3Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel;
- 4Flow Cytometry Unit, Department of Biological Services, The Weizmann Institute of Science, Rehovot 76100, Israel
- Corresponding authors: moshe.oren{at}weizmann.ac.il, yael.aylon{at}weizmann.ac.il
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↵5 These authors contributed equally to this work.
Abstract
p53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in nontransformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-κB subunit. Moreover, it partly shifts p53's conformation and transcriptional output toward a state resembling cancer-associated p53 mutants and endows p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are frequently down-regulated in breast cancer; we propose that such down-regulation might benefit cancer by converting p53 from a tumor suppressor into a tumor facilitator.
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Footnotes
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.268185.115.
- Received July 2, 2015.
- Accepted October 23, 2015.
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