{"id":77798,"date":"2022-10-10T14:54:44","date_gmt":"2022-10-10T12:54:44","guid":{"rendered":"https:\/\/www.pcb.ub.edu\/scientists-develop-a-study-model-for-ewing-sarcoma-in-the-drosophila-fly\/"},"modified":"2022-10-11T17:15:37","modified_gmt":"2022-10-11T15:15:37","slug":"scientists-develop-a-study-model-for-ewing-sarcoma-in-the-drosophila-fly","status":"publish","type":"post","link":"https:\/\/www.pcb.ub.edu\/en\/scientists-develop-a-study-model-for-ewing-sarcoma-in-the-drosophila-fly\/","title":{"rendered":"Scientists develop a study model for Ewing sarcoma in the Drosophila fly"},"content":{"rendered":"

Researchers led by Dr. Cayetano Gonz\u00e1lez, ICREA research professor at IRB Barcelona<\/a>, located at the Barcelona Science Park, and Dr. Jaume Mora, scientific director at the SJD Pediatric Cancer Center Barcelona<\/a>, have engineered Drosophila transgenic strains that express a mutant variant of the human oncogene called EWS-FLIFS. This is an unprecedented animal model that can be used to investigate Ewing sarcoma and to screen for compounds that may serve as lead molecules for the development of therapeutic drugs. The work has been published in PNAS Nexus.<\/strong><\/p>\n

Ewing sarcoma is the second most frequent bone tumour in children, adolescents, and young adults. There is no specific treatment for this disease and current management is still limited to surgery, radiotherapy, and chemotherapy. The long-term survival of patients with metastatic or relapsed Ewing sarcoma is very low.<\/p>\n

Ewing sarcoma is caused by a single oncogene that results from the fusion of two genes. Although a variety of genes may be involved, EWSR1 and FLI1 and the resulting cancer-driving oncogene, known as EWS-FLI, are found to be responsible in the majority of patients. Unlike most other types of cancer, all attempts to develop experimental animal models of Ewing sarcoma in mice (expressing the EWS-FLI oncogene) have failed.<\/p>\n

Prompted by the need for a genetically tractable model that could be used to study the disease, researchers led by\u00a0Dr. Cayetano Gonz\u00e1lez<\/strong>, ICREA research professor at IRB Barcelona, and\u00a0Dr. Jaume Mora<\/strong>, scientific director at the SJD Pediatric Cancer Center Barcelona (PCCB), have engineered Drosophila transgenic strains that express a mutant variant of the human oncogene called EWS-FLIFS. Remarkably, they have found that expression of the human EWS-FLIFS protein in certain types of Drosophila cells triggers the same oncogenic pathways known to account for EWS-FLI oncogenic activity in human patients.<\/p>\n

\"\"

Source: IRB Barcelona.<\/p><\/div>\n

Lighting up two oncogenic pathways<\/strong><\/h3>\n

Building upon their new transgenic Drosophila line, the authors have rewired two oncogenic pathways used by EWS-FLI, such that when triggered by the presence of EWS-FLIFS, they result in the expression of a fluorescent protein that would otherwise never be expressed. Thus, rather than tumour growth, the researchers use fluorescence as a read-out of EWS-FLI oncogenic activity.<\/p>\n

\u201cThis simple genetic trick greatly facilitates the implementation of massive genetic and chemical screens to identify “modifiers” that inhibit EWS-FLI’s oncogenic activity as inhibitors of the appearance of fluorescence,\u201d explains\u00a0Dr. Cristina Molnar<\/strong>, a postdoctoral researcher at IRB Barcelona and first author of the study.<\/p>\n

Genetic screens based on this new model will make it possible to discover critical proteins required for EWS-FLI to exert its oncogenic function, hence expanding our knowledge of the molecular basis of the disease, as well as identifying new putative therapeutic targets.\u00a0 Chemical screens may identify compounds that could serve as lead molecules for the development of therapeutic drugs.<\/p>\n

\u00bb More information: IRB Barcelona website [+]<\/a><\/strong><\/p>\n

\u00bb Reference article:<\/strong>\u00a0Cristina Molnar, Jose Reina, Anastasia Herrero, Jan Peter Heinen, Victoria M\u00e9ndiz, Sophie Bonnal, Manuel Irimia, Mar\u00eda S\u00e1nchez-Jim\u00e9nez, Sara S\u00e1nchez-Molina, Jaume Mora, Cayetano Gonzalez, Human EWS-FLI protein recapitulates in Drosophila the neomorphic functions that induce Ewing sarcoma tumorigenesis,\u00a0PNAS Nexus<\/em>, 2022;, pgac222,\u00a0https:\/\/doi.org\/10.1093\/pnasnexus\/pgac222<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Researchers led by Dr. Cayetano Gonz\u00e1lez, ICREA research professor at IRB Barcelona, located at the Barcelona Science Park, and Dr. Jaume Mora, scientific director at the SJD Pediatric Cancer Center…<\/p>\n","protected":false},"author":4,"featured_media":77789,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[36],"tags":[],"class_list":["post-77798","post","type-post","status-publish","format-standard","has-post-thumbnail","category-science"],"acf":[],"yoast_head":"\nScientists develop a study model for Ewing sarcoma in the Drosophila fly - Parc Cient\u00edfic de Barcelona<\/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:\/\/www.pcb.ub.edu\/en\/scientists-develop-a-study-model-for-ewing-sarcoma-in-the-drosophila-fly\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Scientists develop a study model for Ewing sarcoma in the Drosophila fly - 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