دورية أكاديمية
Epithelial TGFβ engages growth-factor signalling to circumvent apoptosis and drive intestinal tumourigenesis with aggressive features.
| العنوان: | Epithelial TGFβ engages growth-factor signalling to circumvent apoptosis and drive intestinal tumourigenesis with aggressive features. |
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| المؤلفون: | Flanagan DJ; Cancer Research UK Beatson Institute, Glasgow, UK. dustin.flanagan@monash.edu.; Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia. dustin.flanagan@monash.edu.; Cancer Program, Biomedicine Discovery Institute, Monash University, Melbourne, Australia. dustin.flanagan@monash.edu., Amirkhah R; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., Vincent DF; Cancer Research UK Beatson Institute, Glasgow, UK., Gunduz N; Cancer Research UK Beatson Institute, Glasgow, UK., Gentaz P; Cancer Research UK Beatson Institute, Glasgow, UK., Cammareri P; Cancer Research UK Beatson Institute, Glasgow, UK., McCooey AJ; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., McCorry AMB; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., Fisher NC; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., Davis HL; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK., Ridgway RA; Cancer Research UK Beatson Institute, Glasgow, UK., Lohuis J; Department of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Leach JDG; Cancer Research UK Beatson Institute, Glasgow, UK.; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK., Jackstadt R; Cancer Research UK Beatson Institute, Glasgow, UK.; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH) and Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany., Gilroy K; Cancer Research UK Beatson Institute, Glasgow, UK., Mariella E; Department of Oncology, University of Torino, Candiolo, Torino, Italy., Nixon C; Cancer Research UK Beatson Institute, Glasgow, UK., Clark W; Cancer Research UK Beatson Institute, Glasgow, UK., Hedley A; Cancer Research UK Beatson Institute, Glasgow, UK.; University of Newcastle upon Tyne, Newcastle, UK., Markert EK; Cancer Research UK Beatson Institute, Glasgow, UK.; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK., Strathdee D; Cancer Research UK Beatson Institute, Glasgow, UK., Bartholin L; INSERM Centre de Recherche en Cancérologie de Lyon, Lyon, France., Redmond KL; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., Kerr EM; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., Longley DB; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., Ginty F; GE Global Research Center, Niskayuna, NY, USA., Cho S; GE Global Research Center, Niskayuna, NY, USA., Coleman HG; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.; Centre for Public Health, Queen's University Belfast, Belfast, UK., Loughrey MB; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.; Centre for Public Health, Queen's University Belfast, Belfast, UK.; Department of Cellular Pathology, Belfast Health and Social Care Trust, Belfast, UK., Bardelli A; Department of Oncology, University of Torino, Candiolo, Torino, Italy., Maughan TS; CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK., Campbell AD; Cancer Research UK Beatson Institute, Glasgow, UK., Lawler M; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., Leedham SJ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK., Barry ST; Bioscience, Oncology R&D, AstraZeneca, Cambridge, UK., Inman GJ; Cancer Research UK Beatson Institute, Glasgow, UK.; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK., van Rheenen J; Department of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Dunne PD; Cancer Research UK Beatson Institute, Glasgow, UK.; The Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., Sansom OJ; Cancer Research UK Beatson Institute, Glasgow, UK. o.sansom@beatson.gla.ac.uk.; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. o.sansom@beatson.gla.ac.uk. |
| المصدر: | Nature communications [Nat Commun] 2022 Dec 07; Vol. 13 (1), pp. 7551. Date of Electronic Publication: 2022 Dec 07. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
| مواضيع طبية MeSH: | Transforming Growth Factor beta* , Apoptosis*/genetics, Humans |
| مستخلص: | The pro-tumourigenic role of epithelial TGFβ signalling in colorectal cancer (CRC) is controversial. Here, we identify a cohort of born to be bad early-stage (T1) colorectal tumours, with aggressive features and a propensity to disseminate early, that are characterised by high epithelial cell-intrinsic TGFβ signalling. In the presence of concurrent Apc and Kras mutations, activation of epithelial TGFβ signalling rampantly accelerates tumourigenesis and share transcriptional signatures with those of the born to be bad T1 human tumours and predicts recurrence in stage II CRC. Mechanistically, epithelial TGFβ signalling induces a growth-promoting EGFR-signalling module that synergises with mutant APC and KRAS to drive MAPK signalling that re-sensitise tumour cells to MEK and/or EGFR inhibitors. Together, we identify epithelial TGFβ signalling both as a determinant of early dissemination and a potential therapeutic vulnerability of CRC's with born to be bad traits. (© 2022. The Author(s).) |
| التعليقات: | Erratum in: Nat Commun. 2023 Jan 31;14(1):522. (PMID: 36720858) |
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(PMID: 10.1038/s41467-019-08586-3) |
| معلومات مُعتمدة: | 110371/Z/15/Z United Kingdom WT_ Wellcome Trust; MR/S021205/1 United Kingdom MRC_ Medical Research Council; 24387 United Kingdom CRUK_ Cancer Research UK; BB/T002824/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; A12481 United Kingdom CRUK_ Cancer Research UK; MC_PC_21042 United Kingdom MRC_ Medical Research Council; MR/R017247/1 United Kingdom MRC_ Medical Research Council; 26045 United Kingdom CRUK_ Cancer Research UK; MC_PC_17117 United Kingdom MRC_ Medical Research Council; MR/M016587/1 United Kingdom MRC_ Medical Research Council; 15333 United Kingdom CRUK_ Cancer Research UK; 29834 United Kingdom CRUK_ Cancer Research UK; R01 CA208179 United States CA NCI NIH HHS; A17196 United Kingdom CRUK_ Cancer Research UK; 206314/Z/17/Z United Kingdom WT_ Wellcome Trust; G0400302 United Kingdom MRC_ Medical Research Council; 29802 United Kingdom CRUK_ Cancer Research UK |
| المشرفين على المادة: | 0 (Transforming Growth Factor beta) |
| تواريخ الأحداث: | Date Created: 20221208 Date Completed: 20221215 Latest Revision: 20240320 |
| رمز التحديث: | 20240320 |
| مُعرف محوري في PubMed: | PMC9729215 |
| DOI: | 10.1038/s41467-022-35134-3 |
| PMID: | 36477656 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 2041-1723 |
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| DOI: | 10.1038/s41467-022-35134-3 |