دورية أكاديمية
Epigenomic landscape of human colorectal cancer unveils an aberrant core of pan-cancer enhancers orchestrated by YAP/TAZ
| العنوان: | Epigenomic landscape of human colorectal cancer unveils an aberrant core of pan-cancer enhancers orchestrated by YAP/TAZ |
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| المؤلفون: | Della Chiara G., Gervasoni F., Fakiola M., Godano C., D'Oria C., Azzolin L., Bonnal R. J. P., Moreni G., Drufuca L., Rossetti G., Ranzani V., Bason R., De Simone M., Panariello F., Ferrari I., Fabbris T., Zanconato F., Forcato M., Romano O., Caroli J., Gruarin P., Sarnicola M. L., Cordenonsi M., Bardelli A., Zucchini N., Ceretti A. P., Mariani N. M., Cassingena A., Sartore-Bianchi A., Testa G., Gianotti L., Opocher E., Pisati F., Tripodo C., Macino G., Siena S., Bicciato S., Piccolo S., Pagani M. |
| المساهمون: | Della Chiara G., Gervasoni F., Fakiola M., Godano C., D'Oria C., Azzolin L., Bonnal R.J.P., Moreni G., Drufuca L., Rossetti G., Ranzani V., Bason R., De Simone M., Panariello F., Ferrari I., Fabbris T., Zanconato F., Forcato M., Romano O., Caroli J., Gruarin P., Sarnicola M.L., Cordenonsi M., Bardelli A., Zucchini N., Ceretti A.P., Mariani N.M., Cassingena A., Sartore-Bianchi A., Testa G., Gianotti L., Opocher E., Pisati F., Tripodo C., Macino G., Siena S., Bicciato S., Piccolo S., Pagani M. |
| سنة النشر: | 2021 |
| المجموعة: | Università degli studi di Torino: AperTo (Archivio Istituzionale ad Accesso Aperto) |
| مصطلحات موضوعية: | Adaptor Proteins, Signal Transducing, Colorectal Neoplasm, Gene Expression Regulation, Neoplastic, Histone Code, Human, Models, Genetic, Organoid, RNA-Seq, Single-Cell Analysi, Trans-Activator, Transcription Factor, Tumor Cells, Cultured, Enhancer Elements, Epigenesis |
| الوصف: | Cancer is characterized by pervasive epigenetic alterations with enhancer dysfunction orchestrating the aberrant cancer transcriptional programs and transcriptional dependencies. Here, we epigenetically characterize human colorectal cancer (CRC) using de novo chromatin state discovery on a library of different patient-derived organoids. By exploring this resource, we unveil a tumor-specific deregulated enhancerome that is cancer cell-intrinsic and independent of interpatient heterogeneity. We show that the transcriptional coactivators YAP/TAZ act as key regulators of the conserved CRC gained enhancers. The same YAP/TAZ-bound enhancers display active chromatin profiles across diverse human tumors, highlighting a pan-cancer epigenetic rewiring which at single-cell level distinguishes malignant from normal cell populations. YAP/TAZ inhibition in established tumor organoids causes extensive cell death unveiling their essential role in tumor maintenance. This work indicates a common layer of YAP/TAZ-fueled enhancer reprogramming that is key for the cancer cell state and can be exploited for the development of improved therapeutic avenues. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/33879786; info:eu-repo/semantics/altIdentifier/wos/WOS:000642509600009; volume:12; issue:1; firstpage:2340; lastpage:2358; numberofpages:19; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/2318/1792718Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85104785818 |
| DOI: | 10.1038/s41467-021-22544-y |
| الإتاحة: | https://doi.org/10.1038/s41467-021-22544-yTest http://hdl.handle.net/2318/1792718Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.20354926 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-021-22544-y |
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