Oncogenic ETS fusions promote DNA damage and proinflammatory responses via pericentromeric RNAs in extracellular vesicles

• Published in: The Journal of clinical investigation Vol. 134; no. 9; pp. 1 - 15
• Main Authors: Ruzanov, Peter, Evdokimova, Valentina, Pachva, Manideep C, Minkovich, Alon, Zhang, Zhenbo, Langman, Sofya, Gassmann, Hendrik, Thiel, Uwe, Orlic-Milacic, Marija, Zaidi, Syed H, Peltekova, Vanya, Heisler, Lawrence E, Sharma, Manju, Cox, Michael E, McKee, Trevor D, Zaidi, Mark, Lapouble, Eve, McPherson, John D, Delattre, Olivier, Radvanyi, Laszlo, Burdach, Stefan Eg, Stein, Lincoln D, Sorensen, Poul H
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.05.2024
• Subjects: Animals; Breast cancer; Causes of; Cell Line, Tumor; Cell organelles; Development and progression; DNA; DNA binding proteins; DNA Damage; Ewing's sarcoma; Ewings sarcoma; Extracellular vesicles; Extracellular Vesicles - genetics; Extracellular Vesicles - metabolism; Fibroblasts; Genetic aspects; Genotoxicity; Health aspects; Heterochromatin; Heterochromatin - genetics; Heterochromatin - metabolism; Humans; Inflammation; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Male; Malignancy; Melanoma; Metastases; Metastasis; Mice; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - metabolism; Physiological aspects; Plasma; Plasma levels; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Proteins; Proto-Oncogene Protein c-fli-1 - genetics; Proto-Oncogene Protein c-fli-1 - metabolism; RNA; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; RNA-Binding Protein EWS - genetics; RNA-Binding Protein EWS - metabolism; Sarcoma; Sarcoma, Ewing - genetics; Sarcoma, Ewing - immunology; Sarcoma, Ewing - metabolism; Sarcoma, Ewing - pathology; Scientific equipment and supplies industry; Senescence; Transcription factors; Transcriptional Regulator ERG - genetics; Transcriptional Regulator ERG - metabolism; Tumors; Canada; United States; Ontario; Germany; Innate immunity; Inflammation

Aberrant expression of the E26 transformation-specific (ETS) transcription factors characterizes numerous human malignancies. Many of these proteins, including EWS:FLI1 and EWS:ERG fusions in Ewing sarcoma (EwS) and TMPRSS2:ERG in prostate cancer (PCa), drive oncogenic programs via binding to GGAA r...