MYC-nick promotes cell migration by inducing fascin expression and Cdc42 activation.

MYC-nick is a cytoplasmic, transcriptionally inactive member of the MYC oncoprotein family, generated by a proteolytic cleavage of full-length MYC. MYC-nick promotes migration and survival of cells in response to chemotherapeutic agents or withdrawal of glucose. Here we report that MYC-nick is abundant in colonic and intestinal tumors derived from mouse models with mutations in the Wnt, TGF-β, and PI3K pathways.

p120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification.

E-cadherin-mediated cell-cell adhesion is critical for naive pluripotency of cultured mouse embryonic stem cells (mESCs). E-cadherin-depleted mESC fail to downregulate their pluripotency program and are unable to initiate lineage commitment. To further explore the roles of cell adhesion molecules during mESC differentiation, we focused on p120 catenin (p120ctn).

Ultra-long-term human salt balance studies reveal interrelations between sodium, potassium, and chloride intake and excretion.

Background: The intake of sodium, chloride, and potassium is considered important to healthy nutrition and cardiovascular disease risk. Estimating the intake of these electrolytes is difficult and usually predicated on urine collections, commonly for 24 h, which are considered the gold standard. We reported on data earlier for sodium but not for potassium or chloride.

Inappropriate cadherin switching in the mouse epiblast compromises proper signaling between the epiblast and the extraembryonic ectoderm during gastrulation.

Cadherin switching from E-cadherin (E-cad) to N-cadherin (N-cad) is a key step of the epithelial-mesenchymal transition (EMT) processes that occurs during gastrulation and cancer progression. We investigate whether cadherins actively participate in progression of EMT by crosstalk to signaling pathways. We apply ectopic cadherin switching before the onset of mouse gastrulation.

The Wnt Target Gene L1 in Colon Cancer Invasion and Metastasis.

The Wnt-β-catenin signaling pathway is highly conserved during evolution and determines normal tissue homeostasis. Hyperactivation of Wnt-β-catenin signaling is a characteristic feature of colorectal cancer (CRC) development. β-catenin is a major transducer of the Wnt signal from the cytoplasm into the nucleus where it acts as a co-transcriptional activator of β-catenin-TCF target genes.

CD83 Modulates B Cell Activation and Germinal Center Responses.

CD83 is a maturation marker for dendritic cells. In the B cell lineage, CD83 is expressed especially on activated B cells and on light zone B cells during the germinal center (GC) reaction. The function of CD83 during GC responses is unclear.

ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types.

Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes.

Reactivation of IgG-switched memory B cells by BCR-intrinsic signal amplification promotes IgG antibody production.

Secondary antibody responses are marked by faster kinetics, improved antibody affinity and a switch from IgM to other immunoglobulin isotypes, most notably IgG, compared with primary responses. These changes protect from reinfection and represent the principle of most vaccination strategies. Yet, the molecular mechanisms that underlie B-cell memory responses are unclear.

The MID1 protein is a central player during development and in disease.

Loss-of-function mutations in the MID1 gene cause a rare monogenic disorder, Opitz BBB/G syndrome (OS), which is characterized by malformations of the ventral midline. The MID1 gene encodes the MID1 protein, which assembles a large microtubule-associated protein complex. Intensive research over the past several years has shed light on the function of the MID1 protein as a ubiquitin ligase and regulator of mTOR signalling and translational activator.

The choroid plexus may be an underestimated site of tumor invasion to the brain: an in vitro study using neuroblastoma cell lines.

Background: The central nervous system (CNS) is protected by several barriers, including the blood-brain (BBB) and blood-cerebrospinal fluid (BCSFB) barriers. Understanding how cancer cells circumvent these protective barriers to invade the CNS is of crucial interest, since brain metastasis during cancer is often a fatal event in both children and adults. However, whereas much effort has been invested in elucidating the process of tumor cell transmigration across the BBB, the role of the BCSFB might still be underestimated considering the significant number of meningeal cancer involvement.

Balancing wobbles in the body sodium.

Sodium balance is achieved within a matter of days and everything that enters should come out; sodium stores are of questionable relevance and sodium accumulation is accompanied by weight gain. Careful balance studies oftentimes conflicted with this view, and long-term studies suggested that total body sodium (TBNa) fluctuates independent of intake or body weight. We recently performed the opposite experiment in that we fixed sodium intake for weeks at three levels of sodium intake and collected all urine made.

Chromatin-Remodeling-Factor ARID1B Represses Wnt/β-Catenin Signaling.

The link of chromatin remodeling to both neurodevelopment and cancer has recently been highlighted by the identification of mutations affecting BAF chromatin-remodeling components, such as ARID1B, in individuals with intellectual disability and cancer. However, the underlying molecular mechanism(s) remains unknown. Here, we show that ARID1B is a repressor of Wnt/β-catenin signaling.

The ZEB1/miR-200c feedback loop regulates invasion via actin interacting proteins MYLK and TKS5.

Epithelial to mesenchymal transition (EMT) is a developmental process which is aberrantly activated during cancer invasion and metastasis. Elevated expression of EMT-inducers like ZEB1 enables tumor cells to detach from the primary tumor and invade into the surrounding tissue. The main antagonist of ZEB1 in controlling EMT is the microRNA-200 family that is reciprocally linked to ZEB1 in a double negative feedback loop.

miR-200c dampens cancer cell migration via regulation of protein kinase A subunits.

Expression of miR-200c is a molecular switch to determine cellular fate towards a mesenchymal or epithelial phenotype. miR-200c suppresses the early steps of tumor progression by preventing epithelial-mesenchymal transition (EMT) and intravasation of tumor cells. Unraveling the underlying molecular mechanisms might pinpoint to novel therapeutic options.

Selective Expression of the MAPK Phosphatase Dusp9/MKP-4 in Mouse Plasmacytoid Dendritic Cells and Regulation of IFN-β Production.

Plasmacytoid dendritic cells (pDCs) efficiently produce large amounts of type I IFN in response to TLR7 and TLR9 ligands, whereas conventional DCs (cDCs) predominantly secrete high levels of the cytokines IL-10 and IL-12. The molecular basis underlying this distinct phenotype is not well understood. In this study, we identified the MAPK phosphatase Dusp9/MKP-4 by transcriptome analysis as selectively expressed in pDCs, but not cDCs.

A self-enforcing CD44s/ZEB1 feedback loop maintains EMT and stemness properties in cancer cells.

Invasion and metastasis of carcinomas are often activated by induction of aberrant epithelial-mesenchymal transition (EMT). This is mainly driven by the transcription factor ZEB1, promoting tumor-initiating capacity correlated with increased expression of the putative stem cell marker CD44. However, the direct link between ZEB1, CD44 and tumourigenesis is still enigmatic.

The EMT-activator ZEB1 induces bone metastasis associated genes including BMP-inhibitors.

Tumor cell invasion, dissemination and metastasis is triggered by an aberrant activation of epithelial-to-mesenchymal transition (EMT), often mediated by the transcription factor ZEB1. Disseminating tumor cells must acquire specific features that allow them to colonize at different organ sites. Here we identify a set of genes that is highly expressed in breast cancer bone metastasis and activated by ZEB1.

The temporal expression pattern of alpha-synuclein modulates olfactory neurogenesis in transgenic mice.

Background: Adult neurogenesis mirrors the brain´s endogenous capacity to generate new neurons throughout life. In the subventricular zone/ olfactory bulb system adult neurogenesis is linked to physiological olfactory function and has been shown to be impaired in murine models of neuronal alpha-Synuclein overexpression. We analyzed the degree and temporo-spatial dynamics of adult olfactory bulb neurogenesis in transgenic mice expressing human wild-type alpha-Synuclein (WTS) under the murine Thy1 (mThy1) promoter, a model known to have a particularly high tg expression associated with impaired olfaction.

ZEB1-associated drug resistance in cancer cells is reversed by the class I HDAC inhibitor mocetinostat.

Therapy resistance is a major clinical problem in cancer medicine and crucial for disease relapse and progression. Therefore, the clinical need to overcome it, particularly for aggressive tumors such as pancreatic cancer, is very high. Aberrant activation of an epithelial-mesenchymal transition (EMT) and an associated cancer stem cell phenotype are considered a major cause of therapy resistance.

Adult neurogenesis in neurodegenerative diseases.

Adult neurogenesis is limited to specific brain regions in the mammalian brain, such as the hippocampal dentate gyrus and the subventricular zone/olfactory bulb system. Alterations in adult neurogenesis appear to be a common hallmark in different neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). This is remarkable, because the distinct pathological proteins responsible for the different diseases induce the loss of different neural populations.

miR-148a promotes plasma cell differentiation and targets the germinal center transcription factors Mitf and Bach2.

B cells undergo affinity maturation and class switch recombination of their immunoglobulin receptors during a germinal center (GC) reaction, before they differentiate into long-lived antibody-secreting plasma cells (PCs). Transcription factors such as Bach2 and Mitf are essential during this process, as they delay premature differentiation of GC B cells by repressing Blimp-1 and IRF4, two transcription factors required for terminal PC differentiation. Therefore, Bach2 and Mitf expression must be attenuated in activated B cells to allow terminal PC differentiation, but the precise mechanism remains enigmatic.

Enhancer cooperativity as a novel mechanism underlying the transcriptional regulation of E-cadherin during mesenchymal to epithelial transition.

Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) highlight crucial steps during embryogenesis and tumorigenesis. Induction of dramatic changes in gene expression and cell features is reflected by modulation of Cdh1 (E-cadherin) expression. We show that Cdh1 activity during MET is governed by two enhancers at +7.

Structures of the APC-ARM domain in complexes with discrete Amer1/WTX fragments reveal that it uses a consensus mode to recognize its binding partners.

The tumor suppressor APC employs its conserved armadillo repeat (ARM) domain to recognize many of its binding partners, including Amer1/WTX, which is mutated in Wilms' tumor and bone overgrowth syndrome. The APC-Amer1 complex has important roles in regulating Wnt signaling and cell adhesion. Three sites A1, A2, and A3 of Amer1 have been reported to mediate its interaction with APC-ARM.

The immunoglobulin tail tyrosine motif upgrades memory-type BCRs by incorporating a Grb2-Btk signalling module.

The vigorous response of IgG-switched memory B cells to recurring pathogens involves enhanced signalling from their B-cell antigen receptors (BCRs). However, the molecular signal amplification mechanisms of memory-type BCRs remained unclear. Here, we identify the immunoglobulin tail tyrosine (ITT) motif in the cytoplasmic segments of membrane-bound IgGs (mIgGs) as the principle signal amplification device of memory-type BCRs in higher vertebrates and decipher its signalling microanatomy.