Cancer Institute

  • Keli Xu

    xu_keli.jpgAssistant Professor, Department of Neurobiology & Anatomical Sciences
    Tumor Cell Biology Program
    PhD, Biochemistry, 2001, Rutgers University
    Postdoc, 2001-06, The Hospital for Sick Children, Toronto, Canada

    Contact information
    2500 N State St., Room G757
    Jackson, MS 39216

    Research interests


    • Fringe-modulated Notch signaling in the development and cancer of mammary gland, prostate and lung

    • Cancer stem cells


    Research synopsis

    Breast cancers are heterogeneous at clinical and molecular level. Different subtypes of breast cancer may have different cell-of-origin within mammary epithelial hierarchy. Notch signaling controls mammary epithelial cell fate decision and differentiation. Thus genetic dissection of Notch pathways in the mammary gland may provide insights into intrinsic subtypes of breast cancer. We showed that Lunatic Fringe (Lfng), a glycosyltransferase that modifies Notch receptors thereby modulating Notch activation, regulates mammary stem/progenitor cell activity, and Lfng deficiency cooperates with the Met/Caveolin amplicon to induce basal-like breast cancer. Most recently we defined an oncogenic role for Manic Fringe (Mfng) through Notch-mediated Pik3cg induction in claudin-low breast cancer.

    Elevated Notch ligand and receptor expression has been associated with aggressive forms of prostate cancer, suggesting a role for Notch signaling in prostate tumor initiation and progression. We have reported a critical role for Lfng in regulation of prostate epithelial differentiation and proliferation, as well as in prostate tumor suppression, through differential modulation of Notch receptor activation. We are currently determining roles of Lfng in the pathogenesis of basal- and luminal-originated prostate cancers.

    Notch signaling coordinates a series of events during lung development, including proximodistal fate generation and branching, proximal airway cell fate specification, and alveologenesis. We have found that Jagged1 is the major regulator of Notch-dependent cell fate in proximal airways, and that Lfng-dependent Notch signaling is required for alveologenesis. Notch also plays complex roles in lung carcinogenesis, with the cellular (SCLC vs NSCLC) and microenvironmental (hypoxia) context profoundly affecting tumor cell response to Notch activation. We are interested in identifying Notch pathway genes as biomarker and therapeutic targets for lung cancer.


    Recent accomplishments and honors

    • 2003-06 - Canadian Institutes of Health Research (CIHR) Fellowship

    Selected publications

    • Zhang S, Chung W-C, Wu G, Egan SE, Miele L,Xu K. 2015, Manic Fringe promotes a claudin-low breast cancer phenotype through Notch-mediated PIK3CG induction.Cancer Res.2015 Mar 25. [Epub ahead of print]. PMID: 25808869   
    • Xu K, Bägli DJ, Egan SE. 2014, NOTch just a bladder control problem.Cancer Cell, 26(4): 452-54. PMID: 25314075
    • Zhang S, Chung W-C, Wu G, Egan SE,Xu K. 2014, Tumor suppressive activity of Lunatic Fringe in prostate through differential modulation of Notch receptor activation.Neoplasia. 16(2): 158-167. PMID: 24709423
    • Zhang S, Chung W-C, Miele L,Xu K. 2014, Targeting Met and Notch in theLfng-deficient,Met-amplified triple negative breast cancer.Cancer Biol Ther.15(5): 633-42. PMID: 24556651
    • Zhang S, Loch AJ, Radtke F, Egan SE,Xu K. 2013, Jagged1 is the major regulator of Notch-dependent cell fate in proximal airways.Dev Dyn.242(6): 678-86. PMID: 23526493
    • Xu K, Usary J, Kousis P, Prat A, Wang D-Y, Adams JR, et al. 2012, Lunatic fringe deficiency cooperates with the Met/Caveolin gene amplicon to induce basal-like breast cancer.Cancer Cell.21(5): 626-41. PMCID: PMC3603366
    • Adams JR,Xu K, Liu JC, Agamez NR, Loch AJ, Wong RG, et al. 2011, Cooperation between PIK3Cα and p53 mutations in mouse mammary tumor formation.Cancer Res.71(7):2706-2717. PMID:21324922
    • Yuan JS, Tan JB, Visan I, Matei IR, Urbanellis P,Xu K, et al. 2011, Lunatic Fringe prolongs Delta/Notch-induced self-renewal of committed αβ T-cell progenitors.Blood.117(4):1184-95. PMID:21097675
    • Xu K, Nieuwenhuis E, Cohen BL, Wang W, Canty AJ, Danska JS, et al. 2010, Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis.Am J Physiol Lung Cell Mol Physiol. 298:L45-56. PMCID:PMC2806195
    • Tan JB,Xu K, Cretegny K, Visan I, Yuan JS, Egan SE, et al. 2009, Lunatic and manic fringe cooperatively enhance marginal zone B cell precursor competition for delta-like 1 in splenic endothelial niches.Immunity. 30:254-63. PMID:19217325