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.
Keywords:
COX-2; NFKB2; TP53; cancer; cell migration; homeostasis.
© 2015 Furth et al.; Published by Cold Spring Harbor Laboratory Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Cell Movement / genetics
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / metabolism
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Down-Regulation*
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Gene Expression Regulation, Neoplastic*
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Hippo Signaling Pathway
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Humans
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Mutation
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NF-kappa B p52 Subunit / genetics
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NF-kappa B p52 Subunit / metabolism
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Phosphorylation
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Protein Conformation
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism*
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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Tumor Suppressor Proteins / genetics*
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Tumor Suppressor Proteins / metabolism*
Substances
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NF-kappa B p52 Subunit
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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Cyclooxygenase 2
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PTGS2 protein, human
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LATS1 protein, human
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LATS2 protein, human
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Protein Serine-Threonine Kinases