Zooming in on Long Non-Coding RNAs in Ewing Sarcoma Pathogenesis.

Ewing sarcoma (ES) is a rare aggressive cancer of bone and soft tissue that is mainly characterized by a reciprocal chromosomal translocation. As a result, about 90% of cases express the EWS-FLI1 fusion protein that has been shown to function as an aberrant transcription factor driving sarcomagenesis. ES is the second most common malignant bone tumor in children and young adults.

Mechanisms, Diagnosis and Treatment of Bone Metastases.

Bone and bone marrow are among the most frequent metastatic sites of cancer. The occurrence of bone metastasis is frequently associated with a dismal disease outcome. The prevention and therapy of bone metastases is a priority in the treatment of cancer patients.

MITF reprograms the extracellular matrix and focal adhesion in melanoma.

The microphthalmia-associated transcription factor (MITF) is a critical regulator of melanocyte development and differentiation. It also plays an important role in melanoma where it has been described as a molecular rheostat that, depending on activity levels, allows reversible switching between different cellular states. Here, we show that MITF directly represses the expression of genes associated with the extracellular matrix (ECM) and focal adhesion pathways in human melanoma cells as well as of regulators of epithelial-to-mesenchymal transition (EMT) such as CDH2, thus affecting cell morphology and cell-matrix interactions.

User guide to MiT-TFE isoforms and post-translational modifications.

The microphthalmia-associated transcription factor (MITF) is at the core of melanocyte and melanoma fate specification. The related factors TFEB and TFE3 have been shown to be instrumental for transcriptional regulation of genes involved in lysosome biogenesis and autophagy, cellular processes important for mediating nutrition signals and recycling of cellular materials, in many cell types. The MITF, TFEB, TFE3, and TFEC proteins are highly related.

MITF has a central role in regulating starvation-induced autophagy in melanoma.

The MITF transcription factor is a master regulator of melanocyte development and a critical factor in melanomagenesis. The related transcription factors TFEB and TFE3 regulate lysosomal activity and autophagy processes known to be important in melanoma. Here we show that MITF binds the CLEAR-box element in the promoters of lysosomal and autophagosomal genes in melanocytes and melanoma cells.

Neuregulin-1-mediated ErbB2-ErbB3 signalling protects human trophoblasts against apoptosis to preserve differentiation.

During placentation, foetal trophoblasts invade deeply into maternal tissue to establish a foeto-maternal circulation. We have previously shown that extravillous trophoblast (EVT) lineage cells express ErbB2 and ErbB3, of which the potential as an oncogenic unit is well established. However, a physiological function of this receptor combination in humans remains a puzzling question.

Trophoblast subtype-specific EGFR/ERBB4 expression correlates with cell cycle progression and hyperplasia in complete hydatidiform moles.

Study Question: Do trophoblast subtypes differ in their expression of erythroblastic leukaemia viral oncogene homologue (ERBB) receptor family members and responsiveness towards specific growth factor ligands?

Summary Answer: Our data reveal a reciprocal expression pattern of epidermal growth factor receptor (EGFR)/ERBB4 in proliferative and ERBB2/ERBB3 in invasive trophoblast subtypes, as well as a restricted responsiveness to epidermal growth factor (EGF) and heparin-binding (HB)-EGF.

What Is Known Already: EGFR is expressed by villous cytotrophoblasts (vCTBs), but absent from extravillous trophoblasts (EVTs), which specifically up-regulate ERBB2.

Study Design, Size, Duration: Tissue samples of human first trimester placentae (n = 50) and deciduae (n = 5) obtained from elective pregnancy terminations were used to study trophoblast subtype-specific ERBB receptor expression and responsiveness to recombinant human EGF and HB-EGF.

Extravillous trophoblast-associated ADAM12 exerts pro-invasive properties, including induction of integrin beta 1-mediated cellular spreading.

ADAM12, consisting of a membrane-bound (ADAM12L) and a secreted (ADAM12S) form, is expressed exclusively in regenerating and developing tissue as well as in certain cancer types. Strong ADAM12 expression levels have been noticed in the human placenta, and deregulated ADAM12S levels were associated with various pregnancy-related disorders including pre-eclampsia and intrauterine growth restriction. However, the role of ADAM12 in trophoblast motility has not been investigated so far.

Macrophage-derived IL-33 is a critical factor for placental growth.

IL-33, the most recently discovered member of the IL-1 superfamily and ligand for the transmembrane form of ST2 (ST2L), has been linked to several human pathologies including rheumatoid arthritis, asthma, and cardiovascular disease. Deregulated levels of soluble ST2, the natural IL-33 inhibitor, have been reported in sera of preeclamptic patients. However, the role of IL-33 during healthy pregnancy remains elusive.

Endostatin suppresses IGF-II-mediated signaling and invasion of human extravillous trophoblasts.

Endostatin, a biological active fragment of the extracellular matrix protein collagen XVIII, is known to interfere with cellular motility in the context of pathological angiogenesis. However, the physiological role of endostatin remains largely elusive. Recent evidence suggested that the inhibitor is produced in human decidual cells of early pregnancy, indicating that endostatin could be involved in diverse reproductive processes, such as implantation and/or placental differentiation.