@article{78130c6b192841b9a5b7275856b979b9,
title = "An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis",
abstract = "The epithelial-mesenchymal transition (EMT) and primary ciliogenesis induce stem cell properties in basal mammary stem cells (MaSCs) to promote mammogenesis, but the underlying mechanisms remain incompletely understood. Here, we show that EMT transcription factors promote ciliogenesis upon entry into intermediate EMT states by activating ciliogenesis inducers, including FGFR1. The resulting primary cilia promote ubiquitination and inactivation of a transcriptional repressor, GLIS2, which localizes to the ciliary base. We show that GLIS2 inactivation promotes MaSC stemness, and GLIS2 is required for normal mammary gland development. Moreover, GLIS2 inactivation is required to induce the proliferative and tumorigenic capacities of the mammary tumor-initiating cells (MaTICs) of claudin-low breast cancers. Claudin-low breast tumors can be segregated from other breast tumor subtypes based on a GLIS2-dependent gene expression signature. Collectively, our findings establish molecular mechanisms by which EMT programs induce ciliogenesis to control MaSC and MaTIC stemness, mammary gland development, and claudin-low breast cancer formation.",
author = "Wilson, {Molly M.} and C{\'e}line Callens and {Le Gallo}, Matthieu and Svetlana Mironov and Qiong Ding and Amandine Salamagnon and Chavarria, {Tony E.} and Roselyne Viel and Peasah, {Abena D.} and Arjun Bhutkar and Sophie Martin and Florence Godey and Patrick Tas and Kang, {Hong Soon} and Juin, {Philippe P.} and Jetten, {Anton M.} and Visvader, {Jane E.} and Weinberg, {Robert A.} and Massimo Attanasio and Claude Prigent and Lees, {Jacqueline A.} and Guen, {Vincent J.}",
note = "Funding Information: This work was supported by the MIT Stem Cell Initiative through Fondation MIT, Koch Institute Support (core) grant P30-CA14051 from the National Cancer Institute, Fondation ARC, Canc{\'e}rop{\^o}le Grand Ouest, Universit{\'e} de Rennes 1, SIRIC ILIAD, and Fondation de France. M.M.W. was supported by the David H. Koch Graduate Fellowship. A.M.J. research was supported by the Intramural Research Program of the NIEHS, NIH Z01-ES-101585. V.J.G. was supported by Postdoctoral Fellowships from the Koch Institute and Fondation ARC. Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).",
year = "2021",
month = oct,
doi = "10.1126/sciadv.abf6063",
language = "English (US)",
volume = "7",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "44",
}