The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival

Apoptosis; Endometrial cancer; Map kinaseApoptosis; Cáncer endometrial; Mapa quinasaApoptosi; Càncer d'endometri; Mapa quinasaEndometrial cancer (EC) is the most common type of gynecologic cancer in women of developed countries. Despite surgery combined with chemo-/radiotherapy regimens, overall survival of patients with high-risk EC tumors is poor, indicating a need for novel therapies. The MEK5-ERK5 pathway is activated in response to growth factors and to different stressors, including oxidative stress and cytokines. Previous evidence supports a role for the MEK5-ERK5 pathway in the pathology of several cancers. We investigated the role of ERK5 in EC. In silico analysis of the PanCancer Atlas dataset showed alterations in components of the MEK5-ERK5 pathway in 48% of EC patients. Here, we show that ERK5 inhibition or silencing decreased EGF-induced EC cell proliferation, and that genetic deletion of MEK5 resulted in EC impaired proliferation and reduced tumor growth capacity in nude mice. Pharmacologic inhibition or ERK5 silencing impaired NF-kB pathway in EC cells and xenografts. Furthermore, we found a positive correlation between ERK5 and p65/RELA protein levels in human EC tumor samples. Mechanistically, genetic or pharmacologic impairment of ERK5 resulted in downregulation of NEMO/IKKγ expression, leading to impaired p65/RELA activity and to apoptosis in EC cells and xenografts, which was rescued by NEMO/IKKγ overexpression. Notably, ERK5 inhibition, MEK5 deletion or NF-kB inhibition sensitized EC cells to standard EC chemotherapy (paclitaxel/carboplatin) toxicity, whereas ERK5 inhibition synergized with paclitaxel to reduce tumor xenograft growth in mice. Together, our results suggest that the ERK5-NEMO-NF-κB pathway mediates EC cell proliferation and survival. We propose the ERK5/NF-κB axis as new target for EC treatment.Open Access Funding provided by Universitat Autonoma de Barcelona. The JM Lizcano research group was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO, grant SAF2015-64237-R), and the Spanish Ministry of Science and Innovation (grant PID2019-107561RB-I00), and co-funded by the European Regional Development Fund (ERDF)

Comportamiento perturbador en la adolescencia y su relación con el temperamento y los estilos de afrontamiento

Partiendo de la clasificación del DSM-IV TR que aglutina, bajo la etiqueta de trastornos del comportamiento perturbador, el trastorno de conducta antisocial y el trastorno negativista desafiante, se ha realizado un estudio con dos objetivos: a) conocer las diferencias en la sintomatología del trastorno del comportamiento perturbador durante la adolescencia en función del género, la edad y la ubicación del centro escolar; y b) analizar las relaciones entre las variables temperamentales y de afrontamiento con las dimensiones psicopatológicas de conducta antisocial y negativista desafiante. Se ha administrado el YI-4, el EATQ-R y la ACS a una muestra de 1.240 adolescentes de edades comprendidas entre los 11 y 17 años. Los resultados obtenidos ponen de manifiesto que los chicos realizan un mayor número de conductas antisociales que las chicas, no observándose diferencias según la ubicación del centro escolar. En el caso de la sintomatología negativista desafiante, se observan diferencias según el grupo de edad, siendo a la edad de 13 a 14 años cuando se presenta una mayor sintomatología. Los datos indican una correlación positiva de ambas dimensiones psicopatológicas con surgencia y afrontamiento no productivo y negativa con control voluntario y afrontamiento productivoEmploying the DSM-IV TR classification, which classifies both antisocial behavior disorder and oppositional defiant disorder under the label of disruptive behavior disorder, a study was conducted with two aims: a) to determine the symptomatological differences of disruptive behavior disorder in adolescence depending on gender, age and school location, and b) to analyse the relationships between temperament, coping and the psychopathological dimensions of antisocial and oppositional defiant behavior. The YI-4, EATQ-R and ACS were administered to a sample of 1,240 adolescents between 11 and 17 years of age. The results show that boys display a greater number of antisocial behaviors than girls. No differences in school location were observed. In the oppositional defiant symptoms, there were differences according to age group, with 13 to 14 years being an age when there is a greater symptomatology. The data indicate a positive correlation with psychopathological dimensions of both surgency and non-productive coping and a negative correlation with effortful control and productive copin

Psychometric properties of the EATQ-R among a sample of Catalan-speaking Spanish adolescents

The few studies that have been conducted into the psychometric properties of the EATQ-R, even fewer for the longer version, highlight the fact that its structure differs from that of the original. The aim of this study is to translate and adapt the long version of the EATQ-R to Catalan, study its internal consistency and convergent and factorial validity, and compare differences in the EATQ-R by age and gender. The EATQ-R was administered to a sample of 1481 secondary school students ranging in age from 11 to 17 years. After eliminating 40 items from the 86 comprising the EATQ-R, an adjusted model was obtained with acceptable fit indices comprising 8 of the original 11 factor

The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival

Endometrial cancer (EC) is the most common type of gynecologic cancer in women of developed countries. Despite surgery combined with chemo-/radiotherapy regimens, overall survival of patients with high-risk EC tumors is poor, indicating a need for novel therapies. The MEK5-ERK5 pathway is activated in response to growth factors and to different stressors, including oxidative stress and cytokines. Previous evidence supports a role for the MEK5-ERK5 pathway in the pathology of several cancers. We investigated the role of ERK5 in EC. In silico analysis of the PanCancer Atlas dataset showed altera- tions in components of the MEK5-ERK5 pathway in 48% of EC patients. Here, we show that ERK5 inhibition or silencing decreased EGF-induced EC cell proliferation, and that genetic deletion of MEK5 resulted in EC impaired proliferation and reduced tumor growth capacity in nude mice. Pharmacologic inhibition or ERK5 silencing impaired NF-kB pathway in EC cells and xenografts. Furthermore, we found a positive correlation between ERK5 and p65/RELA protein levels in human EC tumor samples. Mechanistically, genetic or pharmacologic impairment of ERK5 resulted in downregulation of NEMO/ IKKγ expression, leading to impaired p65/RELA activity and to apoptosis in EC cells and xenografts, which was rescued by NEMO/IKKγ overexpression. Notably, ERK5 inhibition, MEK5 deletion or NF-kB inhibition sensitized EC cells to standard EC chemotherapy (paclitaxel/carboplatin) toxicity, whereas ERK5 inhibition synergized with paclitaxel to reduce tumor xenograft growth in mice. Together, our results suggest that the ERK5-NEMO-NF-κB pathway mediates EC cell prolifera- tion and survival. We propose the ERK5/NF-κB axis as new target for EC treatment.The online version contains supplementary material available at 10.1007/s00018-022-04541-

What leads subjective well-being to change throughout adolescence? : an exploration of potential factors

This article presents the results of a one-year follow-up study on a sample of 940 adolescents, in which participants have been classified according to the changes they have experienced in their subjective well-being (SWB), measured by means of two different single-item scales (overall life satisfaction –OLS– and happiness overall – HOL). A range of multinomial logistic regression models were employed to determine which factors lead to such differences. Results show that when OLS is considered, the factor most contributing to an increase in SWB is family self-concept, while the one most contributing to its decrease is satisfaction with the family. When HOL is taken as the dependent variable, the most important factor in predicting an increase in SWB is being valued in the future according to the amount of money I have, with life optimism being the most important factor in predicting its decrease. Only three indicators (the importance of being valued in the future according to the amount of money I have, feeling happy at home and satisfaction with myself) contribute to explaining both boys’ and girls’ models when OLS is taken as the dependent variable, while only one indicator (satisfaction with standard of living) is shared in both boys’ and girls’ models when HOL is the dependent variable. The resulting implications for adolescent SWB are discussed

What leads subjective well-being to change throughout adolescence? : an exploration of potential factors

This article presents the results of a one-year follow-up study on a sample of 940 adolescents, in which participants have been classified according to the changes they have experienced in their subjective well-being (SWB), measured by means of two different single-item scales (overall life satisfaction –OLS– and happiness overall – HOL). A range of multinomial logistic regression models were employed to determine which factors lead to such differences. Results show that when OLS is considered, the factor most contributing to an increase in SWB is family self-concept, while the one most contributing to its decrease is satisfaction with the family. When HOL is taken as the dependent variable, the most important factor in predicting an increase in SWB is being valued in the future according to the amount of money I have, with life optimism being the most important factor in predicting its decrease. Only three indicators (the importance of being valued in the future according to the amount of money I have, feeling happy at home and satisfaction with myself) contribute to explaining both boys’ and girls’ models when OLS is taken as the dependent variable, while only one indicator (satisfaction with standard of living) is shared in both boys’ and girls’ models when HOL is the dependent variable. The resulting implications for adolescent SWB are discussed

Comportamiento perturbador en la adolescencia y su relación con el temperamento y los estilos de afrontamiento

Employing the DSM-IV TR classification, which classifies both antisocial behavior disorder and oppositional defiant disorder under the label of disruptive behavior disorder, a study was conducted with two aims: a) to determine the symptomatological differences of disruptive behavior disorder in adolescence depending on gender, age and school location, and b) to analyse the relationships between temperament, coping and the psychopathological dimensions of antisocial and oppositional defiant behavior. The YI-4, EATQ-R and ACS were administered to a sample of 1,240 adolescents between 11 and 17 years of age. The results show that boys display a greater number of antisocial behaviors than girls. No differences in school location were observed. In the oppositional defiant symptoms, there were differences according to age group, with 13 to 14 years being an age when there is a greater symptomatology. The data indicate a positive correlation with psychopathological dimensions of both surgency and non-productive coping and a negative correlation with effortful control and productive copingPartiendo de la clasificación del DSM-IV TR que aglutina, bajo la etiqueta de trastornos del comportamiento perturbador, el trastorno de conducta antisocial y el trastorno negativista desafiante, se ha realizado un estudio con dos objetivos: a) conocer las diferencias en la sintomatología del trastorno del comportamiento perturbador durante la adolescencia en función del género, la edad y la ubicación del centro escolar; y b) analizar las relaciones entre las variables temperamentales y de afrontamiento con las dimensiones psicopatológicas de conducta antisocial y negativista desafiante. Se ha administrado el YI-4, el EATQ-R y la ACS a una muestra de 1. 240 adolescentes de edades comprendidas entre los 11 y 17 años. Los resultados obtenidos ponen de manifiesto que los chicos realizan un mayor número de conductas antisociales que las chicas, no observándose diferencias según la ubicación del centro escolar. En el caso de la sintomatología negativista desafiante, se observan diferencias según el grupo de edad, siendo a la edad de 13 a 14 años cuando se presenta una mayor sintomatología. Los datos indican una correlación positiva de ambas dimensiones psicopatológicas con surgencia y afrontamiento no productivo y negativa con control voluntario y afrontamiento productiv

Psicothema

Resumen tomado de la publicaciónPartiendo de la clasificación del DSM-IV TR que aglutina, bajo la etiqueta de trastornos del comportamiento perturbador, el trastorno de conducta antisocial y el trastorno negativista desafiante, se ha realizado un estudio con dos objetivos: a) conocer las diferencias en la sintomatología del trastorno del comportamiento perturbador durante la adolescencia en función del género, la edad y la ubicación del centro escolar; y b) analizar las relaciones entre las variables temperamentales y de afrontamiento con las dimensiones psicopatológicas de conducta antisocial y negativista desafiante. Se ha administrado el YI-4, el EATQ-R y la ACS a una muestra de 1.240 adolescentes de edades comprendidas entre los 11 y 17 años. Los resultados obtenidos ponen de manifiesto que los chicos realizan un mayor número de conductas antisociales que las chicas, no observándose diferencias según la ubicación del centro escolar. En el caso de la sintomatología negativista desafiante, se observan diferencias según el grupo de edad, siendo a la edad de 13 a 14 años cuando se presenta una mayor sintomatología. Los datos indican una correlación positiva de ambas dimensiones psicopatológicas con surgencia y afrontamiento no productivo y negativa con control voluntario y afrontamiento productivo.AsturiasColegio Oficial de Psicólogos de Asturias; Calle Ildefonso Sánchez del Río, 4-1 B; 33001 Oviedo; Tel. +34985285778; Fax +34985281374;Universidad de Oviedo. Facultad de Psicología; Plaza Feijoo, s. n.; 33003 Oviedo; Tel. +34985104146; Fax +34985104126;ES

Psychometric properties of the EATQ-R among a sample of Catalan-speaking Spanish adolescents

The few studies that have been conducted into the psychometric properties of the EATQ-R, even fewer for the longer version, highlight the fact that its structure differs from that of the original. The aim of this study is to translate and adapt the long version of the EATQ-R to Catalan, study its internal consistency and convergent and factorial validity, and compare differences in the EATQ-R by age and gender. The EATQ-R was administered to a sample of 1481 secondary school students ranging in age from 11 to 17 years. After eliminating 40 items from the 86 comprising the EATQ-R, an adjusted model was obtained with acceptable fit indices comprising 8 of the original 11 factor