Author/Authors :
Xu، نويسنده , , Keli and Usary، نويسنده , , Jerry and Kousis، نويسنده , , Philaretos C. and Prat، نويسنده , , Aleix and Wang، نويسنده , , Dong-Yu and Adams، نويسنده , , Jessica R. and Wang، نويسنده , , Wei and Loch، نويسنده , , Amanda J. and Deng، نويسنده , , Tao and Zhao، نويسنده , , Wei and Cardiff، نويسنده , , Robert Darrell and Yoon، نويسنده , , Keejung and Gaiano، نويسنده , , Nicholas and Ling، نويسنده , , Vicki and Beyene، نويسنده , , Joseph and Zacksenhaus، نويسنده , , Eldad and Gridley، نويسنده , , Tom and Leong، نويسنده , , Wey L. and Guidos، نويسنده , , Cynthia J. and Perou، نويسنده , , Charles M. and Egan، نويسنده , , Sean E.، نويسنده ,
Abstract :
Summary
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.
