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

作者:Furth Noa; Ben Moshe Noa Bossel; Pozniak Yair; Porat Ziv; Geiger Tamar; Domany Eytan; Aylon Yael; Oren Moshe*
来源:Genes & Development, 2015, 29(22): 2325-2330.
DOI:10.1101/gad.268185.115

摘要

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 non-transformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-kappa B 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.

  • 出版日期2015-11-15