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  • 1
    Keywords: EXPRESSION ; CHROMATIN ; CARCINOMA CELLS ; HUMAN COLON-CANCER ; E-cadherin ; SELF-RENEWAL ; STEM-CELL ; EPITHELIAL-MESENCHYMAL TRANSITION ; INITIATING CELLS ; INTESTINAL EPITHELIUM
    Abstract: EPHB3 is a critical cellular guidance factor in the intestinal epithelium and an important tumor suppressor in colorectal cancer (CRC) whose expression is frequently lost at the adenoma-carcinoma transition when tumor cells become invasive. The molecular mechanisms underlying EPHB3 silencing are incompletely understood. Here we show that EPHB3 expression is anti-correlated with inducers of epithelial-mesenchymal transition (EMT) in primary tumors and CRC cells. In vitro, SNAIL1 and SNAIL2, but not ZEB1, repress EPHB3 reporter constructs and compete with the stem cell factor ASCL2 for binding to an E-box motif. At the endogenous EPHB3 locus, SNAIL1 triggers the displacement of ASCL2, p300 and the Wnt pathway effector TCF7L2 and engages corepressor complexes containing HDACs and the histone demethylase LSD1 to collapse active chromatin structure, resulting in rapid downregulation of EPHB3. Beyond its impact on EPHB3, SNAIL1 deregulates markers of intestinal identity and stemness and in vitro forces CRC cells to undergo EMT with altered morphology, increased motility and invasiveness. In xenotransplants, SNAIL1 expression abrogated tumor cell palisading and led to focal loss of tumor encapsulation and the appearance of areas with tumor cells displaying a migratory phenotype. These changes were accompanied by loss of EPHB3 and CDH1 expression. Intriguingly, SNAIL1-induced phenotypic changes of CRC cells are significantly impaired by sustained EPHB3 expression both in vitro and in vivo. Altogether, our results identify EPHB3 as a novel target of SNAIL1 and suggest that disabling EPHB3 signaling is an important aspect to eliminate a roadblock at the onset of EMT processes.
    Type of Publication: Journal article published
    PubMed ID: 25277775
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of statistical physics 96 (1999), S. 1125-1161 
    ISSN: 1572-9613
    Keywords: spontaneous symmetry breaking ; Goldstone theorem ; normal coordinates ; interacting Bose gases ; Bose–Einstein condensation ; quantum fluctuations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Spontaneous symmetry breaking (SSB) is one of the basic aspects of collective phenomena such as phase transitions in statistical mechanics or ground-state excitations in field theory. In general, spectral analysis of SSB is related to the presence of a Goldstone boson particle. The explicit construction of the canonical variables (boson field operator and its adjoint) of this boson has so far been an open problem. In this paper, we consider the SSB of Bose–Einstein condensation in two models: the so-called imperfect or mean field Bose gas (which is nothing but a perfect ideal Bose gas including the property of equivalence of ensembles), and the Bogoliubov weakly interacting Bose gas. For both we construct explicitly the Goldstone boson field variables. The remarkable result is that in both cases the field and its adjoint field are formed as the “fluctuation operators” respectively of the order parameter operator and of the generator of the broken symmetry. The notion of “fluctuation operator” is essential for our mathematical construction. We find that although the order parameter has a critical fluctuation, the generator of the broken symmetry has a squeezed fluctuation of the same inverse rate. Furthermore, we prove that this canonical pair of variables decouples from the other variables of the system, and that these fluctuations behave dynamically as long-wavelength sound waves or as oscillator variables.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    Journal of Mathematical Physics 40 (1999), S. 1268-1279 
    ISSN: 1089-7658
    Source: AIP Digital Archive
    Topics: Mathematics , Physics
    Notes: The imperfect Boson gas supplemented with a gentle repulsive interaction is completely solved. In particular, it is proved that it has nonextensive Bose–Einstein condensation, i.e., there is condensation without macroscopic occupation of the ground (k=0) state level. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
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