Xu, KeliUsary, JerryKousis, Philaretos C.Prat Aparicio, AleixWang, Dong-YuAdams, Jessica R.Wang, WeiLoch, Amanda J.Deng, TaoZhao, WeiCardiff, Robert D.Yoon, KeejungGaiano, NicholasLing, VickiBeyene, JosephZacksenhaus, EldadGridley, TomLeong, Wey L.Guidos, CynthiaPerou, Charles M.Egan, Sean E.2016-10-052016-10-052012-05-151535-6108https://hdl.handle.net/2445/102376Basal-like breast cancers (BLBC) express a luminal progenitor gene signature. Notch receptor signaling promotes luminal cell fate specification in the mammary gland, while suppressing stem cell self-renewal. Here we show that deletion of Lfng, a sugar transferase that prevents Notch activation by Jagged ligands, enhances stem/progenitor cell proliferation. Mammary-specific deletion of Lfng induces basal-like and claudin-low tumors with accumulation of Notch intracellular domain fragments, increased expression of proliferation-associated Notch targets, amplification of the Met/Caveolin locus, and elevated Met and Igf-1R signaling. Human BL breast tumors, commonly associated with JAGGED expression, elevated MET signaling, and CAVEOLIN accumulation, express low levels of LFNG. Thus, reduced LFNG expression facilitates JAG/NOTCH luminal progenitor signaling and cooperates with MET/CAVEOLIN basal-type signaling to promote BLBC.24 p.application/pdfeng(c) Elsevier, 2012Càncer de mamaExpressió gènicaTransducció de senyal cel·lularProteïnes de membranaBreast cancerGene expressionCellular signal transductionMembrane proteinsinfo:eu-repo/semantics/article6625962016-10-05info:eu-repo/semantics/openAccess22624713