Lunatic Fringe Deficiency Cooperates with the Met/Caveolin Gene Amplicon to Induce Basal-like Breast Cancer Journal Articles uri icon

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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.


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

publication date

  • May 2012

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