Investigadors del grup de Gens i C\u00e0ncer del Programa d’Epigen\u00e8tica i Biologia del C\u00e0ncer de l’Institut d’Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL) han descobert que el gen MAX est\u00e0 inactivat gen\u00e8ticament en el c\u00e0ncer de pulm\u00f3 de c\u00e8l\u00b7lula petita i que la seva restituci\u00f3 redueix molt significativament el creixement cel\u00b7lular . <\/p>\n
Aquesta troballa posa de manifest que MAX actua com a gen supressor de tumors en un dels tipus de c\u00e0ncer pulmonar m\u00e9s agressius i amb pitjor pron\u00f2stic. Els resultats d’aquest estudi s’han publicat a la revista Cancer Discovery <\/p>\n
A m\u00e9s d’identificar el paper supressor tumoral de MAX en c\u00e0ncer de pulm\u00f3, el grup dirigit per Montse Sanchez-Cespedes ha observat una relaci\u00f3 funcional entre MAX i un altre supressor tumoral, BRG1, en virtut de la qual BRG1 regula l’expressi\u00f3 de MAX. No obstant aix\u00f2, la connexi\u00f3 funcional \u00e9s encara m\u00e9s complexa. D’una banda, la pres\u00e8ncia de BRG1 \u00e9s necess\u00e0ria perqu\u00e8 MAX pugui activar moltes de les seves dianes, incloent-hi gens relacionats amb el metabolisme de la glucosa i gens de diferenciaci\u00f3 neuroendocrina. <\/p>\n
D’altra banda, l’eliminaci\u00f3 de BRG1 en c\u00e8l\u00b7lules canceroses que no tenen MAX produeix mortalitat cel\u00b7lular, el que suggereix una interacci\u00f3 letal sint\u00e8tica entre ambdues prote\u00efnes. Aix\u00f2 succeeix \u00fanicament en l\u00ednies cel\u00b7lulars de c\u00e0ncer pulm\u00f3 amb mutacions en MAX i no en aquelles altres que tenen activaci\u00f3 dels oncogens MYC. Aquesta interacci\u00f3 del tipus letal sint\u00e8tic \u00e9s especialment rellevant des del punt de vista cl\u00ednic ja que inhibidors de l’activitat de BRG1 podrien constituir una ter\u00e0pia efectiva en pacients amb c\u00e0ncer de pulm\u00f3 de c\u00e8l\u00b7lula petita amb mutacions inactivadores de MAX . <\/p>\n
L’equip de Sanchez-Cespedes ha identificat diversos gens alterats en c\u00e0ncer pulmonar. Entre ells destaca BRG1 (tamb\u00e9 anomenat SMARCA4) que est\u00e0 inactivat de forma general en molts tipus de c\u00e0ncer. El grup de Sanchez-Cespedes havia demostrat pr\u00e8viament que la p\u00e8rdua de BRG1 est\u00e0 \u00edntimament relacionada amb l’activaci\u00f3 de MYC. Ambdues alteracions s\u00f3n m\u00fatuament excloents i actuen permetent la p\u00e8rdua de diferenciaci\u00f3 cel\u00b7lular durant el desenvolupament del c\u00e0ncer de pulm\u00f3 . <\/p>\n
El nou descobriment que MAX actua com un gen supressor tumoral en c\u00e0ncer de pulm\u00f3 recolza l’exist\u00e8ncia d’una connexi\u00f3 funcional entre el complex SWI\/SNF i els complexos MYC\/MAX en el control de la diferenciaci\u00f3 cel\u00b7lular i el desenvolupament del c\u00e0ncer de pulm\u00f3 . <\/p>\n
Refer\u00e8ncia de l\u2019article<\/span> <\/p>\n <\/span> Romero OA, Torres-Diz M, Pros E, Savola S, Gomez A, Moran S, Saez C, Iwakawa R, Villanueva A, Montuenga LM, Kohno T, Yokota J, Sanchez-Cespedes M.MAX inactivation in small-cell lung cancer disrupts the MYC-SWI\/SNF programs and is synthetic lethal with BRG1. Cancer Discov. 2013 Dec 20. [Epub ahead of print]. <\/p>\n Romero OA, Sanchez-Cespedes M.The SWI\/SNF genetic blockade: effects in cell differentiation, cancer and developmental diseases. Oncogene. 2013 Jun 10. [Epub ahead of print] <\/p>\n Romero OA, Setien F, John S, Gimenez-Xavier P, G\u00f3mez-L\u00f3pez G, Pisano D, Condom E, Villanueva A, Hager GL, Sanchez-Cespedes M.The tumour suppressor and chromatin-remodelling factor BRG1 antagonizes Myc activity and promotes cell differentiation in human cancer.EMBO Mol Med. 2012 Jul;4(7):603-16. <\/p>\n <\/span><\/p>\n","protected":false},"excerpt":{"rendered":" Investigadors del grup de Gens i C\u00e0ncer del Programa d’Epigen\u00e8tica i Biologia del C\u00e0ncer de l’Institut d’Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL) han descobert que el gen MAX est\u00e0 inactivat gen\u00e8ticament en el c\u00e0ncer de pulm\u00f3 de c\u00e8l\u00b7lula petita i que la seva restituci\u00f3 redueix molt significativament el creixement cel\u00b7lular . Aquesta troballa posa de manifest […]<\/p>\n","protected":false},"author":6,"featured_media":11061,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"no-sidebar","site-content-layout":"page-builder","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":"default","adv-header-id-meta":"","stick-header-meta":"default","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 center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[1],"tags":[],"class_list":["post-8450","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-sin-categorizar"],"publishpress_future_action":{"enabled":false,"date":"2024-11-25 09:17:58","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/8450","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/comments?post=8450"}],"version-history":[{"count":0,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/8450\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media\/11061"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media?parent=8450"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/categories?post=8450"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/tags?post=8450"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}