{"id":88695,"date":"2021-11-03T16:55:42","date_gmt":"2021-11-03T15:55:42","guid":{"rendered":"https:\/\/ibecbarcelona.eu\/?p=88695"},"modified":"2021-11-17T16:48:00","modified_gmt":"2021-11-17T15:48:00","slug":"el-gen-ras-i-la-fisica-actuen-conjuntament-en-processos-cancerigens","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/el-gen-ras-i-la-fisica-actuen-conjuntament-en-processos-cancerigens\/","title":{"rendered":"El gen RAS i la f\u00edsica actuen conjuntament en processos cancer\u00edgens"},"content":{"rendered":"

\u00a0<\/span><\/h3>\n
\"\"
Retracci\u00f3 d’un epiteli transformat amb RAS des del pla fins a la massa cancerosa. Font: Vito Conte Lab.<\/span><\/span><\/figcaption><\/figure>\n

El c\u00e0ncer \u00e9s una fam\u00edlia complexa de m\u00e9s de 200 malalties diferents, not\u00f2riament dif\u00edcils d’estudiar i tractar. Aix\u00f2 \u00e9s degut en part a la gran quantitat de mutacions gen\u00e8tiques que causen c\u00e0ncer, on cada forma de la malaltia interromp els processos cel\u00b7lulars i moleculars de diferents maneres. Entre ells hi ha el gen RAS, la mutaci\u00f3 del qual passa al voltant del 30% dels c\u00e0ncers humans, i se sap que causa la p\u00e8rdua de l’arquitectura fisiol\u00f2gica dels epitelis. Els epitelis s\u00f3n teixits importants del nostre organisme i produeixen les formes m\u00e9s agressives de c\u00e0ncer: els carcinomes. Encara estem reconstruint com l’activaci\u00f3 oncog\u00e8nica condueix a la p\u00e8rdua de la morfologia epitelial, i cada cop hi ha m\u00e9s proves que apunten que la f\u00edsica dels teixits \u00e9s un vincle important que falta.<\/span><\/span>\u00a0<\/span><\/p>\n

 <\/p>\n

Ara, un nou estudi dirigit per Vito Conte (<\/span><\/span>IBEC<\/span><\/span><\/a>\u00a0i\u00a0<\/span><\/span>TU\/e<\/span><\/span><\/a>) ha proporcionat m\u00e9s informaci\u00f3 sobre com la f\u00edsica dels teixits\u00a0<\/span>media<\/span>\u00a0l’expressi\u00f3 d’oncogens i la p\u00e8rdua de l’arquitectura dels teixits a les primeres etapes del desenvolupament del tumor. \u201c<\/strong><\/span><\/span>Sab\u00edem que el c\u00e0ncer altera la f\u00edsica dels teixits\u201d, diu Conte. \u201cAra estem comprenent gradualment que la f\u00edsica dels teixits tamb\u00e9\u00a0<\/span>retroalimenta<\/span>\u00a0la progressi\u00f3 del c\u00e0ncer. Aquesta reciprocitat obre noves vies per enfortir les ter\u00e0pies actuals o fins i tot per dissenyar-ne de noves, com en el cas de la\u00a0<\/span>mecanoterap\u00e8utica<\/span>\u201d.<\/span><\/span>\u00a0<\/span><\/strong><\/p>\n

Comen\u00e7ant amb una capa de c\u00e8l\u00b7lules normals<\/span><\/span>\u00a0<\/span><\/strong><\/h3>\n

Les c\u00e8l\u00b7lules de l’epiteli operen de manera altament coordinada per mantenir l’arquitectura i la morfologia que el teixit requereix per fer la seva funci\u00f3.<\/span>\u00a0<\/span><\/p>\n

La p\u00e8rdua d’aquest equilibri i la ruptura posterior de l’arquitectura dels teixits s\u00f3n un segell distintiu dels tumors que comencen a l’epiteli, que representen fins al 90% de tots els c\u00e0ncers.<\/span>\u00a0<\/span><\/p>\n

Conte i el seu equip internacional d’investigadors van estudiar com la f\u00edsica est\u00e0 involucrada en aquest proc\u00e9s quan l’oncog\u00e8n\u202fRAS s’activa en una sola capa de c\u00e8l\u00b7lules epitelials<\/span>. “Identificar canvis mec\u00e0nics\u202fen l’\u00e0mbit cel\u00b7lular\u202fdirectament al cos hum\u00e0 \u00e9s dif\u00edcil. Aleshores, el nostre principal desafiament va ser desenvolupar una forma de fer cr\u00e9ixer teixit hum\u00e0 normal al laboratori i despr\u00e9s\u202fmonitorar\u202fen temps real l’estructura i la mec\u00e0nica dels tumors en aquests teixits quan activem l’oncog\u00e8n\u202fRAS”, assenyala la Dra.\u202fAgata\u202fNyga, primera autora de\u202fl’estudi.<\/span><\/b>\u00a0<\/span><\/p>\n

Transformant el component maligne de 2D a 3<\/span>D<\/span><\/span><\/strong>\u00a0<\/span>
<\/span><\/h3>\n

Els investigadors van cultivar capes 2D de c\u00e8l\u00b7lules epitelials al laboratori i van activar l’oncog\u00e8n\u202fRAS en mostres seleccionades. En nom\u00e9s 24 hores, l’activaci\u00f3 oncog\u00e8nica va induir inestabilitat estructural i mec\u00e0nica als teixits en desequilibrar les forces intercel\u00b7lulars altament controlades que donen als epitelis la seva funci\u00f3 de barrera. En\u00a0menys de 48 hores, els teixits on RAS estava activat s’havien transformat en massa 3D, indicatiu de l’inici del creixement tumoral.<\/span>\u00a0<\/span><\/p>\n

D’altra banda, les mostres d’epitelis no transformats van mantenir la seva estructura en 2D en forma de capa, com ara el control. Una inspecci\u00f3 m\u00e9s propera de les mostres amb l’oncog\u00e8n\u202fRAS activat va revelar que les c\u00e8l\u00b7lules s’havien separat primer en dues capes discretes, que preparaven tot el teixit per contraure’s i formar una massa cancerosa 3D. Els investigadors van donar suport a les seves troballes modelant les dades en una simulaci\u00f3 per ordinador.<\/span>\u00a0<\/span><\/p>\n

“El nostre estudi va mostrar que el canvi\u202fd’una\u202festructura 2D a 3D est\u00e0 controlat per un mecanisme f\u00edsic espec\u00edfic del teixit transformat per RAS. Aix\u00f2 significa que totes les c\u00e8l\u00b7lules transformades amb RAS que formen el teixit han de coordinar el seu esfor\u00e7 mec\u00e0nic de manera f\u00edsica espec\u00edfica per provocar el canvi morfol\u00f2gic. Si entenem per qu\u00e8 i com passa aix\u00f2, \u00e9s possible que els canvis f\u00edsics d’aquest tipus es puguin utilitzar com a marcadors del comen\u00e7ament del c\u00e0ncer en el futur, que despr\u00e9s podrien ser l’objectiu de les mecanoter\u00e0pies”, assenyala Conte.<\/span>\u00a0<\/span><\/p>\n

“L’evid\u00e8ncia experimental que\u202fdona\u202fsuport a la naturalesa mec\u00e0nica del c\u00e0ncer s’est\u00e0 tornant aclaparadora i l’escepticisme del passat amb qu\u00e8 s’han tractat aquestes idees ha comen\u00e7at a retrocedir”, diu Conte<\/span><\/span><\/strong>. “No obstant aix\u00f2, encara tenim feina per fer per conv\u00e8ncer completament la comunitat d’investigadors de c\u00e0ncer (i als consells de recerca que financen la nostra recerca) que\u00a0<\/span><\/span>cal un enfocament m\u00e9s inclusiu per estudiar el c\u00e0ncer: un enfocament que combini la mec\u00e0nica amb la bioqu\u00edmica, immunologia i biologia molecular”.<\/span><\/span>\u00a0<\/span><\/strong><\/p>\n

En menys de 48 hores, els teixits on el gen RAS estava activat s’havien transformat en massa 3D, indicatiu de l’inici del creixement tumoral.<\/span><\/span><\/strong><\/p>\n

Vito Conte\u00a0<\/strong><\/p>\n<\/blockquote>\n

\u00a0<\/span><\/p>\n

Article de refer\u00e8ncia: <\/span><\/b>\u00a0<\/span><\/p>\n

Agata\u00a0Nyga, Jose J. Mu\u00f1oz, Suze\u00a0Dercksen, Giulia Fornabaio, Marina\u00a0Uroz, Xavier\u00a0Trepat, Buzz Baum, Helen K. Matthews and Vito Conte.\u00a0<\/span>Oncogenic\u202fRAS\u202finstructs morphological transformation of human epithelia via differential tissue mechanics<\/span><\/a>.\u00a0Science Advances, 2021.<\/span>\u00a0<\/span><\/p>\n

\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Investigadors de l’IBEC\u202fi la UPC (Espanya),\u202fUCL\u202f(Regne Unit) i TU\/e (Pa\u00efsos Baixos) demostren que l’activaci\u00f3 de l’oncog\u00e8n\u202fRAS indueix caracter\u00edstiques tumorals als teixits a trav\u00e9s de canvis f\u00edsics. Publicat a la revista cient\u00edfica Science\u202fAdvances, el nou treball suggereix que els futurs tractaments contra el c\u00e0ncer haurien d’apuntar tant als processos biol\u00f2gics subjacents a la malaltia, com a l’estructura mec\u00e0nica en evoluci\u00f3 del teixit afectat. <\/h3>\n","protected":false},"author":4,"featured_media":88175,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[96],"tags":[],"post_formats":[],"class_list":["post-88695","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticies-de-recerca"],"yoast_head":"\nEl gen RAS i la f\u00edsica actuen conjuntament en processos cancer\u00edgens - Institute for Bioengineering of Catalonia<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ibecbarcelona.eu\/ca\/el-gen-ras-i-la-fisica-actuen-conjuntament-en-processos-cancerigens\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"El gen RAS i la f\u00edsica actuen conjuntament en processos cancer\u00edgens - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"Investigadors de l'IBEC\u202fi la UPC (Espanya),\u202fUCL\u202f(Regne Unit) i TU\/e (Pa\u00efsos Baixos) demostren que l'activaci\u00f3 de l'oncog\u00e8n\u202fRAS indueix caracter\u00edstiques tumorals als teixits a trav\u00e9s de canvis f\u00edsics. 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