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Lunatic Fringe Deficiency Cooperates with the Met/Caveolin Gene Amplicon to Induce Basal-Like Breast Cancer
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Basal-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.
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XU, Keli, USARY, Jerry, KOUSIS, Philaretos c., PRAT APARICIO, Aleix, WANG, Dong-yu, ADAMS, Jessica r., WANG, Wei, LOCH, Amanda j., DENG, Tao, ZHAO, Wei, CARDIFF, Robert d., YOON, Keejung, GAIANO, Nicholas, LING, Vicki, BEYENE, Joseph, ZACKSENHAUS, Eldad, GRIDLEY, Tom, LEONG, Wey l., GUIDOS, Cynthia, PEROU, Charles m., EGAN, Sean e.. Lunatic Fringe Deficiency Cooperates with the Met/Caveolin Gene Amplicon to Induce Basal-Like Breast Cancer. _Cancer Cell_. 2012. Vol. 21, núm. 5, pàgs. 626-641. [consulta: 28 de gener de 2026]. ISSN: 1535-6108. [Disponible a: https://hdl.handle.net/2445/102376]