Our previous study reported that Epstein-Barr virus(EBV)-encoded latent membrane protein 1 (LMP1) could induce development of CD44(+/High) stem-like cells in nasopharyngeal carcinoma (NPC). However, ...the molecular mechanisms that underlie modulation of cancer stem cells (CSCs) in NPC remain unclear. Here, we show that LMP1 induced CSC-like properties through promotion of the expression of epithelial-mesenchymal transition-like cellular markers and through alterations in differentiation markers. Furthermore, LMP1 activated and triggered phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, which subsequently stimulated expression of CSC markers, development of side population and tumor sphere formation. This suggests that PI3K/AKT pathway has an important role in the induction and maintenance of CSC properties in NPC. Similarly, PI3K/AKT pathway was also activated by phosphorylase in LMP1-induced CD44(+/High) cells. In addition, LMP1 greatly increased expression of miR-21 and downregulated expression of the miR-21 target, PTEN. Overexpression of miR-21 by transfection of miR-21 mimics into LMP1-transformed cells led to phosphorylase-mediated activation of the PI3K/AKT pathway and induction of CSCs. On the contrary, phosphorylation of the PI3K/AKT pathway and the expression of CSC were reversed by an miR-21 inhibitor. The specific inhibitor (Ly294002) of PI3K/AKT pathway significantly decreased expression of miR-21 and CSC markers and upregulated the expression of PTEN, which indicates that miR-21 and PTEN are the downstream effectors of PI3K/AKT and that expression of these two effectors are related to the development of NPC CSCs. Taken together, our novel findings indicate that LMP1, PI3K/AKT, miR-21 and PTEN constitute a positive feedback loop and have a key role in LMP1-induced CSCs in NPC.
The Spitzer Extended Deep Survey (SEDS) is a very deep infrared survey within five well-known extragalactic science fields: the UKIDSS Ultra-Deep Survey, the Extended Chandra Deep Field South, ...COSMOS, the Hubble Deep Field North, and the Extended Groth Strip. SEDS covers a total area of 1.46 deg super(2) to a depth of 26 AB mag (3sigma) in both of the warm Infrared Array Camera (IRAC) bands at 3.6 and 4.5 mum. Because of its uniform depth of coverage in so many widely-separated fields, SEDS is subject to roughly 25% smaller errors due to cosmic variance than a single-field survey of the same size. SEDS was designed to detect and characterize galaxies from intermediate to high redshifts (z = 2-7) with a built-in means of assessing the impact of cosmic variance on the individual fields. Because the full SEDS depth was accumulated in at least three separate visits to each field, typically with six-month intervals between visits, SEDS also furnishes an opportunity to assess the infrared variability of faint objects. This paper describes the SEDS survey design, processing, and publicly-available data products. Deep IRAC counts for the more than 300,000 galaxies detected by SEDS are consistent with models based on known galaxy populations. Discrete IRAC sources contribute 5.6 + or - 1.0 and 4.4 + or - 0.8 nW m super(-2) sr super(-1) at 3.6 and 4.5 mum to the diffuse cosmic infrared background (CIB). IRAC sources cannot contribute more than half of the total CIB flux estimated from DIRBE data. Barring an unexpected error in the DIRBE flux estimates, half the CIB flux must therefore come from a diffuse component.
Kruppel-like factor 4 (KLF4) is highly expressed in more than 70% of breast cancers and functions as an oncogene. However, an exact mechanism by which KLF4 enhances tumorigenesis of breast cancer ...remains unknown. In this study, we show that KLF4 was highly expressed in cancer stem cell (CSC)-enriched populations in mouse primary mammary tumor and breast cancer cell lines. Knockdown of KLF4 in breast cancer cells (MCF-7 and MDA-MB-231) decreased the proportion of stem/progenitor cells as demonstrated by expression of stem cell surface markers such as aldehyde dehydrogenase 1, side population and by in vitro mammosphere assay. Consistently KLF4 overexpression led to an increase of the cancer stem cell population. KLF4 knockdown also suppressed cell migration and invasion in MCF-7 and MDA-MB-231 cells. Furthermore, knockdown of KLF4 reduced colony formation in vitro and inhibited tumorigenesis in immunocompromised non-obese diabetic/severe combined immunodeficiency mice, supporting an oncogenic role for KLF4 in breast cancer development. Further mechanistic studies revealed that the Notch signaling pathway was required for KLF4-mediated cell migration and invasion, but not for CSC maintenance. Taken together, our study provides evidence that KLF4 has a potent oncogenic role in mammary tumorigenesis likely by maintaining stem cell-like features and by promoting cell migration and invasion. Thus, targeting KLF4 may provide an effective therapeutic approach to suppress tumorigenicity in breast cancer.
New sets of parameters (“tunes”) for the underlying-event (UE) modelling of the
pythia
8,
pythia6
and
herwig++
Monte Carlo event generators are constructed using different parton distribution ...functions. Combined fits to CMS UE proton–proton (
p
p
) data at
s
=
7
TeV
and to UE proton–antiproton (
p
p
¯
) data from the CDF experiment at lower
s
, are used to study the UE models and constrain their parameters, providing thereby improved predictions for proton–proton collisions at 13
TeV
. In addition, it is investigated whether the values of the parameters obtained from fits to UE observables are consistent with the values determined from fitting observables sensitive to double-parton scattering processes. Finally, comparisons are presented of the UE tunes to “minimum bias” (MB) events, multijet, and Drell–Yan (
q
q
¯
→
Z
/
γ
∗
→
lepton-antilepton+jets) observables at 7 and 8
TeV
, as well as predictions for MB and UE observables at 13
TeV
.
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