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http://hdl.handle.net/2445/102376
Title: | Lunatic Fringe Deficiency Cooperates with the Met/Caveolin Gene Amplicon to Induce Basal-Like Breast Cancer |
Author: | 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. |
Keywords: | Càncer de mama Expressió gènica Transducció de senyal cel·lular Proteïnes de membrana Breast cancer Gene expression Cellular signal transduction Membrane proteins |
Issue Date: | 15-May-2012 |
Publisher: | Elsevier |
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. |
Note: | Versió postprint del document publicat a: http://dx.doi.org/10.1016/j.ccr.2012.03.041 |
It is part of: | Cancer Cell, 2012, vol. 21, num. 5, p. 626-641 |
URI: | http://hdl.handle.net/2445/102376 |
Related resource: | http://dx.doi.org/10.1016/j.ccr.2012.03.041 |
ISSN: | 1535-6108 |
Appears in Collections: | Articles publicats en revistes (Medicina) |
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