Cell migration is a key process in cancer metastasis, allowing malignant cells to spread from the primary tumor to distant organs. At the molecular level, migration is the result of several coordinated events involving mechanical forces and cellular signaling, where the second messenger Ca 2+ plays a pivotal role. Therefore, elucidating the regulation of intracellular Ca 2+ levels is key for a complete understanding of the mechanisms controlling cellular migration. In this regard, understanding the function of Transient Receptor Potential (TRP) channels, which are fundamental determinants of Ca 2+ signaling, is critical to uncovering mechanisms of mechanotransduction during cell migration and, consequently, in pathologies closely linked to it, such as cancer. Here, we review recent studies on the association between TRP channels and migration-related mechanotransduction events, as well as in the involvement of TRP channels in the migration-dependent pathophysiological process of metastasis.
Transient receptor potential melastatin 4 (TRPM4) is a Ca2+‐activated nonselective cationic channel that regulates cell migration and contractility. Increased TRPM4 expression has been related to pathologies, in which cytoskeletal rearrangement and cell migration are altered, such as metastatic cancer. Here, we identify the K+ channel tetramerization domain 5 (KCTD5) protein, a putative adaptor of cullin3 E3 ubiquitin ligase, as a novel TRPM4‐interacting protein. We demonstrate that KCTD5 is a positive regulator of TRPM4 activity by enhancing its Ca2+ sensitivity. We show that through its effects on TRPM4 that KCTD5 promotes cell migration and contractility. Finally, we observed that both TRPM4 and KCTD5 expression are increased in distinct patterns in different classes of breast cancer tumor samples. Together, these data support that TRPM4 activity can be regulated through expression levels of either TRPM4 or KCTD5, not only contributing to increased understanding of the molecular mechanisms involved on the regulation of these important ion channels, but also providing information that could inform treatments based on targeting these distinct molecules that define TRPM4 activity.
Cell migration is critical for several physiological and pathophysiological processes. It depends on the coordinated action of kinases, phosphatases, Rho-GTPases proteins, and Ca2+ signaling. Interestingly, ubiquitination events have emerged as regulatory elements of migration. Thus, the role of proteins involved in ubiquitination processes could be relevant to a complete understanding of pro-migratory mechanisms. KCTD5 is a member of Potassium Channel Tetramerization Domain (KCTD) proteins that have been proposed as a putative adaptor for Cullin3-E3 ubiquitin ligase and a novel regulatory protein of TRPM4 channels. Here, we study whether KCTD5 participates in cell migration-associated mechanisms, such as focal adhesion dynamics and cellular spreading. Our results show that KCTD5 CRISPR/Cas9- and shRNA-based depletion in B16-F10 cells promoted an increase in cell migration and cell spreading, and a decrease in the focal adhesion area, consistent with an increased focal adhesion disassembly rate. The expression of a dominant-negative mutant of Rho-GTPases Rac1 precluded the KCTD5 depletion-induced increase in cell spreading. Additionally, KCTD5 silencing decreased the serum-induced Ca2+ response, and the reversion of this with ionomycin abolished the KCTD5 knockdown-induced decrease in focal adhesion size. Together, these data suggest that KCTD5 acts as a regulator of cell migration by modulating cell spreading and focal adhesion dynamics through Rac1 activity and Ca2+ signaling, respectively.
Miguel Aguilar Ahumada is a Chilean composer, academic, and musicologist. His value in the Chilean and Latin American musical panorama lies in his role as a key figure for understanding the development of musical institutions outside the main centres of production. His work is a benchmark in the singular transition to Chilean avant-garde music in the mid-twentieth century, particularly as an outstanding example on the adoption of the twelve-tone system. He was instrumental in promoting avant-garde music until the 1973 putsch compromised his ability to maintain his connections in Santiago. Aguilar received the Municipal Prize of Art in Music (1986), the Charles Ives Award for Composers (1996), the Regional Award in Musical Arts (2006), and the President of the Republic Award in the Classical Music category (2006).
Natural killer T (NKT) cells constitute a unique subset of T lymphocytes characterized by specifically interacting with antigenic glycolipids conjugated to the CD1d receptor on antigen-presenting cells. Functionally, NKT cells are capable of performing either effector or suppressor immune responses, depending on their production of proinflammatory or anti-inflammatory cytokines, respectively. Effector NKT cells are subdivided into three subsets, termed NKT1, NKT2, and NKT17, based on the cytokines they produce and their similarity to the cytokine profile produced by Th1, Th2, and Th17 lymphocytes, respectively. Recently, a new subgroup of NKT cells termed NKT10 has been described, which cooperates and interacts with other immune cells to promote immunoregulatory responses. Although the tissue-specific functions of NKT cells have not been fully elucidated, their activity has been associated with the pathogenesis of different inflammatory diseases with immunopathogenic similarities to periodontitis, including osteolytic pathologies such as rheumatoid arthritis and osteoporosis. In the present review, we revise and discuss the pathogenic characteristics of NKT cells in these diseases and their role in the pathogenesis of periodontitis; particularly, we analyze the potential regulatory role of the IL-10-producing NKT10 cells.
en Concepción y la frontera del Biobío, 1957Biobío, -1960 Recopilación, difusión del folklore y desborde creativo. Concepción: Universidad de Concepción, 2016, 356 pp. El sustancioso encuentro entre Violeta Parra y la ciudad de Concepción, materializado en sucesivas visitas y una estadía, fue fruto del afán modernizador que caracterizó a la Universidad de Concepción (UdeC) bajo el liderazgo de David Stitchkin Branover (1956-1962, cuyo ímpetu definió el futuro de la institución. Fue la primera vez que esta casa de estudios se enfrentó a una intención seria y categórica de romper con el persistente hermetismo de la academia y buscar los medios para que el conocimiento fluyera activamente más allá de los límites del campus. Fue él quien quiso poner en contacto a su universidad con aquellos saberes tradicionales que hasta entonces se habían visto excluidos de sus aulas.Esa voluntad ha sido recogida y explorada por la Cátedra Violeta Parra, iniciativa lanzada en 2016 con el respaldo de la Vicerrectoría de Relaciones Institucionales y Vinculación con el Medio de la UdeC. Actuando como mediadora y gestora, se ha dedicado tanto a producir y difundir conocimiento relativo a la celebérrima artista nacional como promover y preservar la cultura tradicional chilena contribuyendo al debate, la reflexión crítica y la divulgación de sus diferentes formas de expresión, inspirándose en el legado de Violeta como referente de la música popular y la investigación. Por supuesto, aprender a enfrentar este desafío siendo fiel a los principios que los motivan es un largo proceso de aprendizaje.Es en ese marco que se nos presenta el libro Violeta Parra en Concepción y la frontera del Biobío: 1957Biobío: -1960. Recopilación, difusión del folklore y desborde creativo, resultado de la investigación realizada por el Dr. Fernando Venegas Espinoza, actual Director del Departamento de Historia de la UdeC y principal responsable de la referida cátedra. Como sugiere el título, este trabajo nos relata los encuentros y desencuentros de sus dos protagonistas: Violeta Parra y la ciudad de Concepción, problematizando el periodo en que la folclorista se relacionó de forma más estrecha con la zona, por medio de la universidad y de su trabajo como recopiladora.El arte de portada del libro ya supone una declaración de principios, un gesto que valida las prácticas populares vigentes recurriendo al muralista Ernesto "Pititore" Guerrero, cuyo estilo gráfico, que recoge elementos del muralismo y el grafiti, es actualmente una marca de identidad urbana en Concepción. Además, aunque en ocasiones resulta difícil abandonar los usos académicos, se procura utilizar un lenguaje simple y transparente que haga el texto accesible a cualquier lector interesado.Como es posible esperar, el libro aporta nuevos antecedentes biográficos de la artista. Pero no se agota en el anecdotario. Por el contrario, Violeta se convierte a ratos en el pretexto para elaborar un relato situado y revisitar un valioso pasaje de la historia local, el de mayor auge cultural en Concepción...
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