ABSTRACT
Correct apicobasal polarization and intercellular adhesions are essential for the appropriate development of normal epithelia. Here, we investigated the contribution of the cell polarity regulator PARD3 to the development of lung squamous cell carcinomas (LSCC). Tumor-specific PARD3 alterations were found in 8% of LSCCs examined, placing PARD3 among the most common tumor suppressor genes in this malignancy. Most PAR3-mutant proteins exhibited a relative reduction in the ability to mediate formation of tight junctions and actin-based protrusions, bind atypical protein kinase C, activate RAC1, and activate STAT3 at cell confluence. Thus, PARD3 alterations prevented the formation of contacts between neighboring cells and the subsequent downstream signaling. Notably, reconstituting PAR3 activity in vivo reduced tumor-invasive and metastatic properties. Our findings define PARD3 as a recurrently inactivated cell polarity regulator in LSCC that affects tumor aggressiveness and metastasis.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Cell Cycle Proteins/genetics , Liver Neoplasms/metabolism , Lung Neoplasms/metabolism , Membrane Proteins/genetics , STAT3 Transcription Factor/metabolism , Adaptor Proteins, Signal Transducing , Animals , Base Sequence , Carcinoma, Squamous Cell/secondary , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Humans , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Membrane Proteins/metabolism , Mice, Nude , Mutation , Neoplasm Invasiveness , Neoplasm Transplantation , Protein Kinase C/metabolism , Sequence Analysis, DNA , Transcriptome , rac1 GTP-Binding Protein/metabolismABSTRACT
Introducción y objetivos: El objetivo principal de este estudio fue comparar los datos estabilométricos del equilibrio unipodal entre el sexo del individuo y la pierna dominante/no dominante de forma estática y dinámica. Participantes: La muestra de estudio fueron 20 sujetos (10 mujeres y 10 varones) físicamente activos de 22,56 ± 5,7 años.Métodos: Se midió la amplitud de la desviación del centro de presiones (CP) mediante una plataforma optométrica utilizando tres tests unipodales de dificultad progresiva: ojos abiertos (OA), ojos cerrados (OC) y salto (S). Resultados: En el equilibrio OA no se encontraron diferencias significativas en la desviación del CP en ninguna de las variables. En la prueba OC se mostraron diferencias significativas entre varones y mujeres en el eje lateral y anteroposterior de la pierna no dominante (p < 0,029 y p < 0,035, respectivamente). Por último, en el caso del salto se encontraron diferencias significativas en la pierna dominante y no dominante sólo en el eje lateral (p < 0,011 y < 0,002, respectivamente). No hubo diferencias significativas entre pierna dominante y no dominante, aunque al analizar por separado ambos sexos se encontraron diferencias en los dos ejes del salto de las mujeres y el eje anteroposterior de los varones en el test unipodal de ojos abiertos. Conclusiones: Las mujeres tendieron a mostrar un mayor equilibrio (menor desviación del CP) en los tests más dinámicos (OC y S) en comparación con los varones. A pesar de no encontrar diferencias entre pierna dominante/no dominante en el total del grupo, sí encontramos que las mujeres mostraban mayor desviación del CP en la pierna no dominante en la recepción del salto(AU)
Introduction and objectives: The main objective of this study was to compare the single leg static and dynamic equilibrium data between gender of subjects and dominant and non-dominant limbs. Participants: A total of 20 physically active subjects, 10 men and 10 women (ages: 22.56 ± 5.7 years).Methods: We measured the mean amplitude of lateral and anteroposterior deviation of the pressure centre (PC) by means of an optometric platform using three single leg tests with progressive difficulty: open eyes (OE), closed eyes (CE) and one leg hop (H). Results: There were no significant differences between men and women in the OE test. The CE test showed significant differences in the anteroposterior and lateral plane in the non-dominant leg (p < 0.029 and p < 0.035, respectively). As regards the H test, the results showed significant differences in dominant and no-dominant leg only in the frontal plane (p < 0.011 and p < 0.002, respectively). There were no significant differences between legs; but when the groups were analysed separately by gender differences were found in both planes of the H test in women and anteroposterior axe of OE test in men. Conclusion: Women tend to show lower PC sway in the more dynamic tests (CE and H) compared to men. Although there were no differences between legs in the total group, it was found that women showed a greater PC sway in the non-dominant leg when landing in the one leg hop test compared with men(AU)
