Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 626-641 |
| Number of pages | 16 |
| Journal | Cancer Cell |
| Volume | 21 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 25 2012 |
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ASJC Scopus subject areas
- Oncology
- Cell Biology
- Cancer Research
Cite this
Lunatic Fringe Deficiency Cooperates with the Met/Caveolin Gene Amplicon to Induce Basal-like Breast Cancer. / 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; Yoon, Keejung; Gaiano, Nicholas; Ling, Vicki; Beyene, Joseph; Zacksenhaus, Eldad; Gridley, Tom; Leong, Wey L.; Guidos, Cynthia J.; Perou, Charles M.; Egan, Sean E.
In: Cancer Cell, Vol. 21, No. 5, 25.05.2012, p. 626-641.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Lunatic Fringe Deficiency Cooperates with the Met/Caveolin Gene Amplicon to Induce Basal-like Breast Cancer
AU - Xu, Keli
AU - Usary, Jerry
AU - Kousis, Philaretos C.
AU - Prat, Aleix
AU - Wang, Dong Yu
AU - Adams, Jessica R.
AU - Wang, Wei
AU - Loch, Amanda J.
AU - Deng, Tao
AU - Zhao, Wei
AU - Cardiff, Robert
AU - Yoon, Keejung
AU - Gaiano, Nicholas
AU - Ling, Vicki
AU - Beyene, Joseph
AU - Zacksenhaus, Eldad
AU - Gridley, Tom
AU - Leong, Wey L.
AU - Guidos, Cynthia J.
AU - Perou, Charles M.
AU - Egan, Sean E.
PY - 2012/5/25
Y1 - 2012/5/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84861398396&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861398396&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2012.03.041
DO - 10.1016/j.ccr.2012.03.041
M3 - Article
C2 - 22624713
AN - SCOPUS:84861398396
VL - 21
SP - 626
EP - 641
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 5
ER -