Reference | 1. Dev Biol. 2018 Jan 15;433(2):310-323. doi: 10.1016/j.ydbio.2017.09.005. Epub 2017
Nov 3.
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β-Catenin acts in a position-independent regeneration response in the simple
eumetazoan Hydra.
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Gufler S(1), Artes B(1), Bielen H(2), Krainer I(1), Eder MK(1), Falschlunger
J(1), Bollmann A(1), Ostermann T(1), Valovka T(3), Hartl M(3), Bister K(3),
Technau U(2), Hobmayer B(4).
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Author information: <br>
(1)Institute of Zoology and Center for Molecular Biosciences, University of
Innsbruck, Austria.
(2)Department of Molecular Evolution and Development, University of Vienna,
Austria.
(3)Institute of Biochemistry and Center for Molecular Biosciences, University of
Innsbruck, Austria.
(4)Institute of Zoology and Center for Molecular Biosciences, University of
Innsbruck, Austria. Electronic address: [email protected].
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Wnt/β-Catenin signaling plays crucial roles in regenerative processes in
eumetazoans. It also acts in regeneration and axial patterning in the simple
freshwater polyp Hydra, whose morphallactic regenerative capacity is unparalleled
in the animal kingdom. Previous studies have identified β-catenin as an early
response gene activated within the first 30min in Hydra head regeneration. Here,
we have studied the role of β-Catenin in more detail. First, we show that nuclear
β-Catenin signaling is required for head and foot regeneration. Loss of nuclear
β-Catenin function blocks head and foot regeneration. Transgenic Hydra tissue, in
which β-Catenin is over-expressed, regenerates more heads and feet. In addition,
we have identified a set of putative β-Catenin target genes by transcriptional
profiling, and these genes exhibit distinct expression patterns in the hypostome,
in the tentacles, or in an apical gradient in the body column. All of them are
transcriptionally up-regulated in the tips of early head and foot regenerates. In
foot regenerates, this is a transient response, and expression starts to
disappear after 12-36h. ChIP experiments using an anti-HydraTcf antibody show Tcf
binding at promoters of these targets. We propose that gene regulatory β-Catenin
activity in the pre-patterning phase is generally required as an early
regeneration response. When regenerates are blocked with iCRT14, initial local
transcriptional activation of β-catenin and the target genes occurs, and all
these genes remain upregulated at the site of both head and foot regeneration for
the following 2-3 days. This indicates that the initial regulatory network is
followed by position-specific programs that inactivate fractions of this network
in order to proceed to differentiation of head or foot structures. brachyury1
(hybra1) has previously been described as early response gene in head and foot
regeneration. The HyBra1 protein, however, appears in head regenerating tips not
earlier than about twelve hours after decapitation, and HyBra1 translation does
not occur in iCRT14-treated regenerates. Foot regenerates never show detectable
levels of HyBra1 protein at all. These results suggest that translational control
mechanisms may play a decisive role in the head- and foot-specific
differentiation phase, and HyBra1 is an excellent candidate for such a key
regulator of head specification.
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2. Cancer Sci. 2017 Jul;108(7):1318-1327. doi: 10.1111/cas.13273. Epub 2017 Jun 6.
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ATP-P2Y2-β-catenin axis promotes cell invasion in breast cancer cells.
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Zhang JL(1)(2), Liu Y(1)(2), Yang H(1)(2), Zhang HQ(3), Tian XX(1)(2), Fang
WG(1)(2).
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Author information: <br>
(1)Department of Pathology, Key Laboratory of Carcinogenesis and Translational
Research (Ministry of Education), School of Basic Medical Sciences, Peking
University Health Science Center, Beijing, China.
(2)Department of Pathology, Peking University Third Hospital, Beijing, China.
(3)Department of Anatomy, Histology and Embryology, Peking University Health
Science Center, Beijing, China.
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Extracellular adenosine 5/’-triphosphate (ATP), secreted by living cancer cells or
released by necrotic tumor cells, plays an important role in tumor invasion and
metastasis. Our previous study demonstrated that ATP treatment in vitro could
promote invasion in human prostate cancer cells via P2Y2, a preferred receptor
for ATP, by enhancing EMT process. However, the pro-invasion mechanisms of ATP
and P2Y2 are still poorly studied in breast cancer. In this study, we found that
P2Y2 was highly expressed in breast cancer cells and associated with human breast
cancer metastasis. ATP could promote the in vitro invasion of breast cancer cells
and enhance the expression of β-catenin as well as its downstream target genes
CD44, c-Myc and cyclin D1, while P2Y2 knockdown attenuated above ATP-driven
events in vitro and in vivo. Furthermore, iCRT14, a β-catenin/TCF complex
inhibitor, could also suppress ATP-driven migration and invasion in vitro. These
results suggest that ATP promoted breast cancer cell invasion via P2Y2-β-catenin
axis. Thus blockade of the ATP-P2Y2-β-catenin axis could suppress the invasive
and metastatic potential of breast cancer cells and may serve as potential
targets for therapeutic interventions of breast cancer.
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3. Virology. 2017 Jan;500:91-95. doi: 10.1016/j.virol.2016.10.014. Epub 2016 Oct 24.
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The β-catenin signaling pathway stimulates bovine herpesvirus 1 productive
infection.
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Zhu L(1), Thunuguntla P(2), Liu Y(3), Hancock M(3), Jones C(4).
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Author information: <br>
(1)Oklahoma State University Center for Veterinary Health Sciences Department of
Veterinary Pathobiology Stillwater, OK 74078, USA; Yangzhou University, College
of Veterinary Medicine and Jiangsu Co-innovation Center for Prevention and
Control of Important Animal Infectious Diseases and Zoonosis, 48 Wenhui East
Road, Yangzhou 225009, China.
(2)Oklahoma State University Center for Veterinary Health Sciences Department of
Veterinary Pathobiology Stillwater, OK 74078, USA.
(3)University of Nebraska, Lincoln School of Veterinary Medicine and Biomedical
Sciences Nebraska Center for Virology Morisson Life Science Center Lincoln, NE
68583-0900, USA.
(4)Oklahoma State University Center for Veterinary Health Sciences Department of
Veterinary Pathobiology Stillwater, OK 74078, USA. Electronic address:
[email protected].
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Bovine herpes virus 1 (BoHV-1), an important bovine pathogen, causes
conjunctivitis and disorders in the upper respiratory tract. Following acute
infection, BoHV1 establishes life-long latency in sensory neurons. Recent studies
demonstrated that viral gene products expressed in trigeminal ganglionic neurons
during latency stabilize β-catenin levels, an important signaling molecule that
interacts with a family of DNA binding proteins (T-cell factors) and subsequently
stimulates transcription. In this study, we provide new evidence demonstrating
that BoHV-1 transiently increased β-catenin protein levels in bovine kidney
(CRIB) cells, but not in rabbit skin cells. β-catenin dependent transcription was
also stimulated by infection of CRIB cells. The β-catenin small molecule
inhibitor (iCRT14) significantly reduced the levels of BoHV-1 virus during
productive infection of CRIB cells and rabbit skin cells. In summary, these
studies suggested the ability of β-catenin to stimulate cell survival and cell
cycle regulatory factors enhances productive infection in non-neuronal cells.
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