RAC1B modulates intestinal tumourigenesis via modulation of WNT and EGFR signalling pathways
| العنوان: | RAC1B modulates intestinal tumourigenesis via modulation of WNT and EGFR signalling pathways |
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| المؤلفون: | George Dickson, Linda Popplewell, Farhat V N Din, Adam E. Hall, Kevin Myant, Malcolm G. Dunlop, Paz Freile, Alfonso Bolado, Caroline V. Billard, Victoria Gudiño, Stuart Aitken, Mark Agostino, David A. Stevenson, Douglas Strathdee, Laura Murphy, Owen J. Sansom, Alex von Kriegsheim, Sebastian Öther-Gee Pohl, John W. Cassidy, Patrizia Cammareri, Colin Nixon, Ann P. Wheeler |
| المساهمون: | Pohl, Sebastian Öther-Gee [0000-0002-4294-9498], Aitken, Stuart [0000-0003-4867-4568], Agostino, Mark [0000-0002-1799-0392], Nixon, Colin [0000-0002-8085-2160], von Kriegsheim, Alex [0000-0002-4952-8573], Wheeler, Ann [0000-0001-8617-827X], Strathdee, Douglas [0000-0003-2959-4327], Sansom, Owen J [0000-0001-9540-3010], Myant, Kevin B [0000-0001-8017-1093], Apollo - University of Cambridge Repository |
| المصدر: | Nature Communications Gudiño, V, Öther-Gee Pohl, S, V Billard, C, Cammareri, P, Bolado Carrancio, A, Aitken, S, Stevenson, D, Hall, A, Agostino, M, Cassidy, J, Nixon, C, von Kriegsheim, A, Friele, P, Popplewell, L, Dickson, G, Murphy, L, Wheeler, A P, Dunlop, M G, Din, F V N, Strathdee, D, J. Sansom, O & Myant, K B 2021, ' Rac1b modulates intestinal tumourigenesis via modulation of Wnt and Egfr signalling pathways ', Nature Communications . https://doi.org/10.1038/s41467-021-22531-3Test Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021) |
| بيانات النشر: | Nature Research, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, rac1 GTP-Binding Protein, 0301 basic medicine, Cancer therapy, Carcinogenesis, Colorectal cancer, Cetuximab, General Physics and Astronomy, Mice, Antineoplastic Agents, Immunological, 0302 clinical medicine, Clinical efficacy, Cancer genetics, Wnt Signaling Pathway, EGFR inhibitors, Mice, Knockout, Egfr signalling, Multidisciplinary, Cancer stem cells, Wnt signaling pathway, Up-Regulation, ErbB Receptors, Gene Expression Regulation, Neoplastic, Cancer therapeutic resistance, 030220 oncology & carcinogenesis, Female, Colorectal Neoplasms, Signal Transduction, medicine.drug, Poor prognosis, Science, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Targeted therapies, Mediator, Cell Line, Tumor, medicine, Animals, Humans, business.industry, Neuropeptides, General Chemistry, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, business |
| الوصف: | Current therapeutic options for treating colorectal cancer have little clinical efficacy and acquired resistance during treatment is common, even following patient stratification. Understanding the mechanisms that promote therapy resistance may lead to the development of novel therapeutic options that complement existing treatments and improve patient outcome. Here, we identify RAC1B as an important mediator of colorectal tumourigenesis and a potential target for enhancing the efficacy of EGFR inhibitor treatment. We find that high RAC1B expression in human colorectal cancer is associated with aggressive disease and poor prognosis and deletion of Rac1b in a mouse colorectal cancer model reduces tumourigenesis. We demonstrate that RAC1B interacts with, and is required for efficient activation of the EGFR signalling pathway. Moreover, RAC1B inhibition sensitises cetuximab resistant human tumour organoids to the effects of EGFR inhibition, outlining a potential therapeutic target for improving the clinical efficacy of EGFR inhibitors in colorectal cancer. RAC1 is a downstream target of the Wnt signaling that promotes intestinal stem cell expansion and tumorigenesis. Here, the authors identify the specific splice variant RAC1B as an important mediator of colorectal tumourigenesis and a potential target for enhancing the efficacy of EGFR inhibitor treatment. |
| وصف الملف: | application/pdf; application/zip; text/xml |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d761f8e664c9c0e74b157a8fb7baff43Test https://eprints.gla.ac.uk/239120/1/239120.pdfTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d761f8e664c9c0e74b157a8fb7baff43 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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