Down-regulation of LATS kinases alters p53 to promote cell migration

Noa Furth, Noa Bossel Ben-Moshe, Yair Pozniak, Ziv Porat, Tamar Geiger, Eytan Domany, Yael Aylon, Moshe Oren*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

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.

Original languageEnglish
Pages (from-to)2325-2330
Number of pages6
JournalGenes and Development
Volume29
Issue number22
DOIs
StatePublished - 15 Nov 2015

Keywords

  • COX-2
  • Cancer
  • Cell migration
  • Homeostasis
  • NFKB2
  • TP53

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