title: Down-regulation of LATS kinases alters p53 to promote cell migration.
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.
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Noa
authors.initials: N
authors.lastname: Furth
authors.affiliation: Department of Physics of Complex Systems, The Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Noa
authors.initials: N
authors.lastname: Bossel Ben-Moshe
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel;
authors.forename: Yair
authors.initials: Y
authors.lastname: Pozniak
authors.affiliation: Flow Cytometry Unit, Department of Biological Services, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Porat
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel;
authors.forename: Tamar
authors.initials: T
authors.lastname: Geiger
authors.affiliation: Department of Physics of Complex Systems, The Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Eytan
authors.initials: E
authors.lastname: Domany
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Yael
authors.initials: Y
authors.lastname: Aylon
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Moshe
authors.initials: M
authors.lastname: Oren
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D000090683:Hippo Signaling Pathway; D006801:Humans; D009154:Mutation; D052003:NF-kappa B p52 Subunit / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D052003:NF-kappa B p52 Subunit; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C092745:LATS1 protein, human; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: COX-2; NFKB2; TP53; cancer; cell migration; homeostasis