@article {27049,
	title = {A new tumor suppressor role for the Notch pathway in bladder cancer},
	journal = {Nat Med},
	volume = {20},
	number = {10},
	year = {2014},
	note = {Rampias, TheodorosVgenopoulou, ParaskeviAvgeris, MargaritisPolyzos, AlexanderStravodimos, KonstantinosValavanis, ChristosScorilas, AndreasKlinakis, ApostolosengResearch Support, Non-U.S. Gov{\textquoteright}t2014/09/10 06:00Nat Med. 2014 Oct;20(10):1199-205. doi: 10.1038/nm.3678. Epub 2014 Sep 7.},
	month = {Oct},
	pages = {1199-205},
	abstract = {The Notch signaling pathway controls cell fates through interactions between neighboring cells by positively or negatively affecting the processes of proliferation, differentiation and apoptosis in a context-dependent manner. This pathway has been implicated in human cancer as both an oncogene and a tumor suppressor. Here we report new inactivating mutations in Notch pathway components in over 40\% of human bladder cancers examined. Bladder cancer is the fourth most commonly diagnosed malignancy in the male population of the United States. Thus far, driver mutations in fibroblast growth factor receptor 3 (FGFR3) and, less commonly, in RAS proteins have been identified. We show that Notch activation in bladder cancer cells suppresses proliferation both in vitro and in vivo by directly upregulating dual-specificity phosphatases (DUSPs), thus reducing the phosphorylation of ERK1 and ERK2 (ERK1/2). In mouse models, genetic inactivation of Notch signaling leads to Erk1/2 phosphorylation, resulting in tumorigenesis in the urinary tract. Collectively our findings show that loss of Notch activity is a driving event in urothelial cancer.},
	keywords = {Animals, Carcinoma, Transitional Cell/genetics/metabolism/pathology, Cell Line, Tumor, Cell Proliferation, Disease Models, Animal, Dual-Specificity Phosphatases/metabolism, Female, Gene Dosage, Genes, Tumor Suppressor, Humans, Male, MAP Kinase Signaling System, Mice, Mutation, Receptor, Notch1/deficiency/genetics/metabolism, Receptors, Notch/deficiency/genetics/*metabolism, signal transduction, Tumor Suppressor Proteins/deficiency/genetics/*metabolism, Urinary Bladder Neoplasms/genetics/*metabolism/pathology},
	isbn = {1546-170X (Electronic)1078-8956 (Linking)},
	author = {Rampias, T. and Vgenopoulou, P. and Avgeris, M. and Polyzos, A. and Stravodimos, K. and Valavanis, C. and Scorilas, A. and Klinakis, A}
}
