{"id":21144,"date":"2014-06-27T09:25:00","date_gmt":"2014-06-27T07:25:00","guid":{"rendered":"https:\/\/www.opc.cat\/unos-40-genes-definen-la-agresividad-en-melanoma-2\/"},"modified":"2014-06-27T09:25:00","modified_gmt":"2014-06-27T07:25:00","slug":"unos-40-genes-definen-la-agresividad-en-melanoma-2","status":"publish","type":"post","link":"https:\/\/www.opc.cat\/es\/unos-40-genes-definen-la-agresividad-en-melanoma-2\/","title":{"rendered":"Unos 40 genes definen la agresividad en melanoma"},"content":{"rendered":"<div class=\"separator\" style=\"clear: both; text-align: center;\">\n<a href=\"http:\/\/static.diariomedico.com\/images\/2014\/06\/26\/imagen-quay-25056096_1.jpg\" imageanchor=\"1\" style=\"clear: left; float: left; margin-bottom: 1em; margin-right: 1em;\"><img fetchpriority=\"high\" decoding=\"async\" border=\"0\" src=\"http:\/\/static.diariomedico.com\/images\/2014\/06\/26\/imagen-quay-25056096_1.jpg\" height=\"178\" width=\"320\" \/><\/a><\/div>\n<p>Investigadores del Centro Nacional de Investigaciones Oncol\u00f3gicas (CNIO) han descubierto m\u00e1s de 40 genes que definen el grado de agresividad del melanoma y que lo distinguen de otros c\u00e1nceres de mal pron\u00f3stico. El hallazgo, que se publica enCancer Cell, ayudar\u00e1 a determinar aspectos \u00fanicos del melanoma que puedan contribuir a establecer el riesgo de desarrollo de met\u00e1stasis.<\/p>\n<p>Los factores descritos, que est\u00e1n aumentados en melanoma, participan en un mecanismo com\u00fan: la formaci\u00f3n de las ves\u00edculas denominadas endosomas. Los endosomas son una maquinaria por la cual las c\u00e9lulas tumorales, mediante endocitosis, pueden incorporar componentes de su entorno y obtener energ\u00eda al degradarlos mediante autofagia. La autofagia sirve tambi\u00e9n como auto-limpieza para eliminar otras prote\u00ednas o componentes celulares da\u00f1ados o que la c\u00e9lula no necesita.<\/p>\n<p>Entre todos los genes que controlan endocitosis, los autores del trabajo se centraron en uno, RAB7, que presenta la mayor acumulaci\u00f3n en las c\u00e9lulas de melanoma. Tras m\u00e1s de seis a\u00f1os de investigaci\u00f3n, el equipo investigador, liderado por Mar\u00eda Soengas, jefa del grupo de Melanoma del CNIO, demostr\u00f3 que RAB7 determina el destino de las c\u00e9lulas del melanoma: con altas concentraciones de RAB7, la autodigesti\u00f3n celular es muy activa y esto permite a las c\u00e9lulas tumorales obtener energ\u00eda, impedir la acumulaci\u00f3n de componentes t\u00f3xicos y as\u00ed dividirse y proliferar.<\/p>\n<p>Cuando RAB7 se reduce, las c\u00e9lulas utilizan los endosomas para reciclado de prote\u00ednas de met\u00e1stasis, favoreciendo su diseminaci\u00f3n por el organismo.<\/p>\n<p>\u00abEncontrar los mecanismos que determinan por qu\u00e9 el melanoma es tan agresivo es muy complejo porque en este tumor se han descrito m\u00e1s de 80.000 mutaciones\u00bb, explica la investigadora del CNIO Direna Alonso Curbelo, primera autora.Definir \u00abla llave del destino de la c\u00e9lula tumoral\u00bb, seg\u00fan Soengas, es solo uno de los muchos aspectos novedosos sobre el melanoma que descubre este trabajo. Demostrar por qu\u00e9 RAB7 se acumula espec\u00edficamente en el melanoma y c\u00f3mo se modula durante la progresi\u00f3n tumoral es muy valioso desde un punto de vista b\u00e1sico, porque permite identificar debilidades espec\u00edficas del melanoma. <br \/>80.000 mutaciones<\/p>\n<p>Este trabajo tambi\u00e9n es relevante para la cl\u00ednica. Una aplicaci\u00f3n es predecir la evoluci\u00f3n del melanoma: los autores demuestran en biopsias tumorales que la cantidad de RAB7 en el tumor cut\u00e1neo define el riesgo de desarrollo de met\u00e1stasis. \u00abEste estudio abre la puerta a que las prote\u00ednas que controlan ves\u00edculas y regulan la autofagia puedan servir como nuevos marcadores de la supervivencia de los pacientes\u00bb.<\/p>\n<p>Adem\u00e1s, estos resultados ayudan a entender el mecanismo de acci\u00f3n de un compuesto que, seg\u00fan descubri\u00f3 el grupo en 2009, es letal para las c\u00e9lulas del melanoma y otros tumores. Este agente, basado en nanopart\u00edculas de ARN, elimina a las c\u00e9lulas actuando precisamente sobre la formaci\u00f3n de ves\u00edculas. \u00abSab\u00edamos c\u00f3mo nuestros nanocomplejos act\u00faan dentro de las c\u00e9lulas tumorales, pero no c\u00f3mo se incorporan selectivamente en ellas\u00bb, indica Soengas.<\/p>\n<p><b>Bioinform\u00e1tica<\/b><\/p>\n<p>El tama\u00f1o de esas mol\u00e9culas requiere que las c\u00e9lulas formen endosomas para atrapar el compuesto. El estudio muestra que la formaci\u00f3n de endosomas (v\u00eda RAB7) es muy activa en c\u00e9lulas tumorales y no en las normales, que no incorporan las nanopart\u00edculas de ARN, reduciendo la posibilidad de efectos t\u00f3xicos.<\/p>\n<p>Esta ha sido una investigaci\u00f3n multidisciplinar en la que han tenido mucho peso nuevas t\u00e9cnicas computacionales para procesar grandes cantidades de datos gen\u00f3micos. El grupo de Bioinform\u00e1tica del CNIO ha sido clave para comparar 900 l\u00edneas celulares de 35 tipos tumorales e identificar aspectos \u00fanicos del melanoma. Las unidades de imagen molecular han permitido analizar mecanismos de formaci\u00f3n de ves\u00edculas con gran resoluci\u00f3n.<\/p>\n<p>Los autores han trabajado con investigadores del Memorial Sloan Kettering Cancer Center, de Nueva York, y con dermat\u00f3logos y pat\u00f3logos del Hospital 12 de Octubre, en Madrid.<\/p>\n<div>\n<\/div>\n<div style=\"text-align: right;\">\n<i>Fuente: <a href=\"http:\/\/genetica.diariomedico.com\/2014\/06\/27\/area-cientifica\/especialidades\/genetica\/40-genes-definen-agresividad-melanoma\" target=\"_blank\">Diario M\u00e9dico<\/a><\/i><\/div>\n","protected":false},"excerpt":{"rendered":"<p>Investigadores del Centro Nacional de Investigaciones Oncol\u00f3gicas (CNIO) han descubierto m\u00e1s de 40 genes que definen el grado de agresividad del melanoma y que lo distinguen de otros c\u00e1nceres de mal pron\u00f3stico. El hallazgo, que se publica enCancer Cell, ayudar\u00e1 a determinar aspectos \u00fanicos del melanoma que puedan contribuir a establecer el riesgo de desarrollo [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":24335,"comment_status":"","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_uag_custom_page_level_css":"","site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center 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