The Development of Linguistic Competences for Employability: A Training Project for Teachers

AbstractEmployability is a new concept that has just appeared in the Spanish educational system. Its rising importance is due to European Union educational policies which aim to provide young people with training that enables them to take part successfully in the present and future working world.This paper argues for the need to develop employability from the very start of formal education, and within this, we highlight the importance of developing linguistic competence among pre-school and primary pupils as a key element for favouring employability.To be able to do so, the teaching staff must be trained using quality education to enable them to work effectively on this competence. In this paper we present how a training program, with a specific European dimension, has been designed by a state school from the Valencian Community, to serve as a model for other schools concerned about the development of a linguistic competence that helps to improve both teachers’ and pupils’ employability

SETD6 mediates selective interaction and genomic occupancy of BRD4 and MITF in melanoma cells

Aberrant transcriptional programs mediate malignant transformation of melanoma, the most aggressive form of skin cancer. The lysine methyltransferase SETD6 has been implicated in regulating transcription, cell adhesion, migration, and other processes in various cancers; however its role in melanoma remains unexplored. We recently reported that SETD6 monomethylates the BRD4 at K99 to selectively regulate transcription of genes involved in mRNA (messenger RNA) translation. Here, we observed that BRD4 methylation at K99 by SETD6 occurs in melanoma cells. Knockout of SETD6 or a point mutation at BRD4-K99 disrupts BRD4 genomic occupancy. In addition, we show that SETD6 interacts with MITF, a master transcription factor in melanocytes and melanoma, and influences the genomic distribution of MITF. Mechanistically, we uncover a novel chromatin-localized interaction between BRD4 and MITF in melanoma. Our data suggest that BRD4 binds MITF in melanoma cells and that this interaction is dependent on both SETD6-mediated methylation of BRD4 and MITF acetylation. This chromatin complex plays a pivotal role in selective recruitment of BRD4 and MITF to different genomic loci in melanoma cells

The lipid droplet protein DHRS3 is a regulator of melanoma cell state

Lipid droplets are fat storage organelles composed of a protein envelope and lipid rich core. Regulation of this protein envelope underlies differential lipid droplet formation and function. In melanoma, lipid droplet formation has been linked to tumor progression and metastasis, but it is unknown whether lipid droplet proteins play a role. To address this, we performed proteomic analysis of the lipid droplet envelope in melanoma. We found that lipid droplet proteins were differentially enriched in distinct melanoma states; from melanocytic to undifferentiated. DHRS3, which converts all-trans-retinal to all-trans-retinol, is upregulated in the MITFLO/undifferentiated/neural crest-like melanoma cell state and reduced in the MITFHI/melanocytic state. Increased DHRS3 expression is sufficient to drive MITFHI/melanocytic cells to a more undifferentiated/invasive state. These changes are due to retinoic acid mediated regulation of melanocytic genes. Our data demonstrate that melanoma cell state can be regulated by expression of lipid droplet proteins which affect downstream retinoid signaling

Single-cell profiling of MC1R-inhibited melanocytes

The human red hair color (RHC) trait is caused by increased pheomelanin (red-yellow) and reduced eumelanin (black-brown) pigment in skin and hair due to diminished melanocortin 1 receptor (MC1R) function. In addition, individuals harboring the RHC trait are predisposed to melanoma development. While MC1R variants have been established as causative of RHC and are a well-defined risk factor for melanoma, it remains unclear mechanistically why decreased MC1R signaling alters pigmentation and increases melanoma susceptibility. Here, we use single-cell RNA sequencing (scRNA-seq) of melanocytes isolated from RHC mouse models to define a MC1R-inhibited Gene Signature (MiGS) comprising a large set of previously unidentified genes which may be implicated in melanogenesis and oncogenic transformation. We show that one of the candidate MiGS genes, TBX3, a well-known anti-senescence transcription factor implicated in melanoma progression, binds both E-box and T-box elements to regulate genes associated with melanogenesis and senescence bypass. Our results provide key insights into further mechanisms by which melanocytes with reduced MC1R signaling may regulate pigmentation and offer new candidates of study toward understanding how individuals with the RHC phenotype are predisposed to melanoma

Hypoxia at 3D organoid establishment selects essential subclones within heterogenous pancreatic cancer

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The protective role of DOT1L in UV-induced melanomagenesis

The DOT1L histone H3 lysine 79 (H3K79) methyltransferase plays an oncogenic role in MLL-rearranged leukemogenesis. Here, we demonstrate that, in contrast to MLL-rearranged leukemia, DOT1L plays a protective role in ultraviolet radiation (UVR)-induced melanoma development. Specifically, the DOT1L gene is located in a frequently deleted region and undergoes somatic mutation in human melanoma. Specific mutations functionally compromise DOT1L methyltransferase enzyme activity leading to reduced H3K79 methylation. Importantly, in the absence of DOT1L, UVR-induced DNA damage is inefficiently repaired, so that DOT1L loss promotes melanoma development in mice after exposure to UVR. Mechanistically, DOT1L facilitates DNA damage repair, with DOT1L-methylated H3K79 involvement in binding and recruiting XPC to the DNA damage site for nucleotide excision repair (NER). This study indicates that DOT1L plays a protective role in UVR-induced melanomagenesis

MITF is a critical regulator of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in malignant melanoma

© 2015 John Wiley & Sons A/S. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in Pigment cell & melanoma research. To access the final edited and published work see https://doi.org/10.1111/pcmr.12414The multifunctional Ig-like carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is neo-expressed in the majority of malignant melanoma lesions. CEACAM1 acts as a driver of tumor cell invasion, and its expression correlates with poor patient prognosis. Despite its importance in melanoma progression, how CEACAM1 expression is regulated is largely unknown. Here, we show that CEACAM1 expression in melanoma cell lines and melanoma tissue strongly correlates with that of the microphthalmia-associated transcription factor (MITF), a key regulator of melanoma proliferation and invasiveness. MITF is revealed as a direct and positive regulator for CEACAM1 expression via binding to an M-box motif located in the CEACAM1 promoter. Taken together, our study provides novel insights into the regulation of CEACAM1 expression and suggests an MITF-CEACAM1 axis as a potential determinant of melanoma progression