Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and several molecular pathways that underlie the molecular tumorigenesis of HNSCC have been identified. Among them, amplification or overexpression of ΔNp63 isoforms is observed in the majority of HNSCCs. Here, we unveiled a ΔNp63-dependent transcriptional program able to regulate the metabolism and the signaling of hyaluronic acid (HA), the major component of the extracellular matrix (ECM). We found that ∆Np63 is capable of sustaining the production of HA levels in cell culture and in vivo by regulating the expression of the HA synthase HAS3 and two hyaluronidase genes, HYAL-1 and HYAL-3. In addition, ∆Np63 directly regulates the expression of CD44, the major HA cell membrane receptor. By controlling this transcriptional program, ∆Np63 sustains the epithelial growth factor receptor (EGF-R) activation and the expression of ABCC1 multidrug transporter gene, thus contributing to tumor cell proliferation and chemoresistance. Importantly, p63 expression is positively correlated with CD44, HAS3, and ABCC1 expression in squamous cell carcinoma datasets and p63-HA pathway is a negative prognostic factor of HNSCC patient survival. Altogether, our data shed light on a ∆Np63-dependent pathway functionally important to the regulation of HNSCC progression.

Squamous cell carcinoma ( SCC ) is a treatment‐refractory tumour which arises from the epithelium of diverse anatomical sites such as oesophagus, head and neck, lung and skin. Accumulating evidence has revealed a number of genomic, clinical and molecular features commonly observed in SCC of distinct origins. Some of these genetic events culminate in fostering the activity of ΔNp63, a potent oncogene which exerts its pro‐tumourigenic effects by regulating specific transcriptional programmes to sustain malignant cell proliferation and survival. In this review, we will describe the genetic and epigenetic determinants underlying ΔNp63 oncogenic activities in SCC , and discuss some relevant transcriptional effectors of ΔNp63, emphasizing their impact in modulating the crosstalk between tumour cells and tumour microenvironment ( TME ).

After lung cancer, breast cancer (BC) is the most frequent cause of cancer death among women, worldwide. Although advances in screening approaches and targeted therapeutic agents have decreased BC incidence and mortality, over the past five years, triple-negative breast cancer (TNBC) remains the breast cancer subtype that displays the worst prognosis, mainly due to the lack of clinically actionable targets. Genetic and molecular profiling has unveiled the high intrinsic heterogeneity of TNBC, with the basal-like molecular subtypes representing the most diffuse TNBC subtypes, characterized by the expression of basal epithelial markers, such as the transcription factor p63. In this review, we will provide a broad picture on the physiological role of p63, in maintaining the basal epithelial identity, as well as its involvement in breast cancer progression, emphasizing its relevance in tumor cell invasion and stemness.

Significance ΔNp63 is a master regulator of skin homeostasis since it finely controls keratinocyte differentiation and proliferation. Here, we provide cellular and molecular evidence demonstrating the functional role of a ΔNp63 interactor, the R-loop–resolving enzyme Senataxin (SETX), in fine-tuning keratinocyte differentiation. We found that SETX physically binds the p63 DNA–binding motif present in two early epidermal differentiation genes, Keratin 1 (KRT1) and ZNF750, facilitating R-loop removal over their 3′ ends and thus allowing efficient transcriptional termination and gene expression. These molecular events translate into the inability of SETX-depleted keratinocytes to undergo the correct epidermal differentiation program. Remarkably, SETX is dysregulated in cutaneous squamous cell carcinoma, suggesting its potential involvement in the pathogenesis of skin disorders.

Accumulating evidence has proved that deregulation of ΔNp63 expression plays an oncogenic role in head and neck squamous cell carcinomas (HNSCCs). Besides p63, the type 1-insulin-like growth factor (IGF) signalling pathway has been implicated in HNSCC development and progression. Most insulin/IGF1 signalling converges intracellularly onto the protein adaptor insulin receptor substrate-1 (IRS-1) that transmits signals from the receptor to downstream effectors, including the PI3K/AKT and the MAPK kinase pathways, which, ultimately, promote proliferation, invasion, and cell survival. Here we report that p63 directly controls IRS1 transcription and cellular abundance and fosters the PI3K/AKT and MAPK downstream signalling pathways. Inactivation of ΔNp63 expression indeed reduces tumour cell responsiveness to IGF1 stimulation, and inhibits the growth potential of HNSCC cells. In addition, a positive correlation was observed between p63 and IRS1 expression in human HNSCC tissue arrays and in publicly available gene expression data. Our findings indicate that aberrant expression of ΔNp63 in HNSSC may act as an oncogenic stimulus by altering the IGF signalling pathway.

Triple negative breast cancers (TNBC) represent the most aggressive and clinically relevant breast carcinomas. On the basis of specific molecular signature, the majority of TNBC can be classified as basal-like breast carcinoma. Here, we report data showing that in basal-like breast carcinoma cells ΔNp63 is capable of sustaining the production of the hyaluronic acid (HA), one of the major component of the extracellular matrix (ECM). At molecular level, we found that ΔNp63 regulates the expression of HA-related genes, such as the HA synthase HAS3, the hyaluronidase HYAL-1 and CD44, the major HA cell membrane receptor. By controlling this pathway, ∆Np63 contributes to maintain the self-renewal of breast cancer stem cells. Importantly, high HAS3 expression is a negative prognostic factor of TNBC patients. Our data suggest that in basal-type breast carcinoma ∆Np63 might favor a HA-rich microenviroment, which can sustain tumor proliferation and stemness.

Resumen: La Disostosis Cleidocraneal (CCD) es un raro trastorno congénito del esqueleto, asociado a hipoplasia o aplasia clavicular, retardo en el cierre de las fontanelas craneales, con tipo braquicéfalos, retraso de la exfoliación de la dentición temporal, erupción retardada de dientes permanentes, presencia de varios supernumerarios y alteraciones morfológicas del maxilar y mandíbula. El trastorno se hereda como una condición autosómica dominante y en el 40% de los casos de la CCD aparece espontáneamente sin una causa genética aparente. El diagnóstico precoz es muy importante para dar a los pacientes las mejores opciones de tratamiento. En este trabajo, se revisó la literatura sobre esta enfermedad, su etiología, diagnóstico precoz, características generales y dentales. Se presenta un paciente con esta condición. Introducción.La disostosis cleidocraneal (CCD) es un síndrome poco frecuente, que sigue un patrón de herencia autosómica dominante con expresividad variable y en la que es común la afectación de varios miembros de una misma familia. 1 El síndrome de disostosis cleidocraneal fue reportado por primera vez por Martin en 1765. 2 Posteriormente, Marie y Sainton independientemente documentaron los criterios de la enfermedad, en 1898. 2, 3 Etiología.La CCD es una condición autosómica dominante de los huesos causado por defecto en el gen de la CBFA I cromosoma 6p21, que contiene los controles de diferenciación de las células precursoras de los osteoblastos y es esencial para la osificación intramembranosa y endocondral. 4,5 Inicialmente se pensó que sólo la osificación intramembranosa estaba afectada, es decir, la osificación de los huesos del cráneo, clavículas y huesos planos, de ahí el nombre cleidocraneal. Ahora se sabe que los huesos de osificación endocondral también se ven afectados, y que es un trastorno generalizado de muchas de las estructuras esqueléticas. 6,7 Es un trastorno que implica una mutación en el factor de transcripción, Runx2/Cbfa1 (básico obligatorio Factor A1, un miembro de la familia Runt de factores de transcripción), ubicado en el cromosoma 6p21. La Cbfa1 gen controla la diferenciación de células precursoras de los osteoblastos, que es esencial para la osificación membranosa, así como osificación endocondral. 8,9 Se sabe que las mutaciones en los receptores del factor de crecimiento fibroblástico 1, 2 y 3 (FGFR1, 2 y 3), así como los factores de transcripción MSX2 y TWIST causa craneosinostosis, y que las mutaciones en el factor de transcripción RUNX2 (CBFA1) causa displasia cleidocraneal. 10, 11, 12

de anchos intercaninos e intermolares en escolares con dentición mixta, Comuna de Contulmo, Chile. J Oral Res 2013; 2(2): 64-67.Resumen: Introducción: El éxito del tratamiento ortodóncico temprano se fundamenta en el conocimiento del desarrollo de la dentición, por lo cual la medición de sus dimensiones en los diferentes estadios de desarrollo se considera como un factor predictor para el tratamiento y rehabilitación de la población. Objetivo: Conocer y evaluar las características cuantitativas de los anchos intercaninos e intermolares según sexo en la población de niños de 6 a 8 años de la Escuela Artística San Luis de Contulmo. Metodología: Estudio cuantitativo, no experimental, de corte transversal, descriptivo y correlacional. La población de estudio correspondió a 48 alumnos de 6 a 8 años seleccionados por muestreo por conveniencia, a los cuales se les tomó modelos de estudio, midiendo y comparando los anchos intercaninos e intermolares. Resultados: Los promedios resultantes de las mediciones efectuadas fueron: distancia intercanina maxilar 33,2 ±2,6 mm en hombres y 32,2 ±2,3 mm en mujeres, respectivamente la distancia intercanina mandibular 27,1 ±2,3 mm y 26, 6 ±1,9 mm, la distancia intermolar maxilar 51,9 ±3,1 y 51,2 ±3,0 mm y la distancia intermolar mandibular 46 ±2,6 y 44,8 ±3,0 mm. Conclusión: Las diferencias entre los anchos intercaninos e intermolares según sexo no son significativas, en cuanto a la edad se observan diferencias significativas entre los 6 y 8 años en el sexo masculino, no así en el femenino. Este estudio representa un interesante punto de partida para el análisis y discusión de futuras investigaciones. Palabras clave: Evaluación cuantitativa, dimensiones transversales, Arco dental/anomalías.Evaluation of intercanine and intermolar widths in students with mixed dentition, Contulmo Commune, Chile.Abstract: Introduction: The early orthodontic treatment success is based on knowledge the development of the dentition, so measuring their dimensions at different stages of development is considered as a predictor for treatment and rehabilitation of the population. Objective: To explore and evaluate the quantitative characteristics of intercanine and intermolar widths by sex in the population of children of 6-8 years of the Escuela Artistica San Luis de Contulmo. Methodology: quantitative study, non-experimental, cross-sectional, descriptive and correlational. The study population corresponded to 48 students from 6 to 8 years selected by probabilistic sampling, unintentional and opportunistic, to which took study models, measuring and comparing intercanine and intermolar widths. Results: The resulting averages of measurements were: maxillary intercanine 33.2 ±2.6 mm in men and 32.2 ±2.3 mm in women, mandibular intercanine distances respectively 27.1 ± 2.3 mm and 26 6 ±1.9 mm, the distance intermolar maxillary 51.9 ±3.1 and 51.2 ±3.0 mm and the distance mandibular intermolar 46 ±2.6 and 44.8 ±3.0 mm. Conclusion: In relation to the difference between intercanine and intermolar widths by sex are n...