Author:
Furth Noa,Bossel Ben-Moshe Noa,Pozniak Yair,Porat Ziv,Geiger Tamar,Domany Eytan,Aylon Yael,Oren Moshe
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.
Funder
Center of Excellence grant
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
Robert Bosch Stiftung
Estate of John Hunter
Cancer Research at the Weizmann Institute
Leir Charitable Foundation
German Research Foundation
Israel Cancer Research Fund
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
66 articles.
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