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The Iroquois homeob...
The Iroquois homeobox proteins IRX3 and IRX5 have distinct roles in Wilms tumour development and human nephrogenesis
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- Holmquist Mengelbier, Linda (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancercellers evolution,Forskargrupper vid Lunds universitet,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Pathways of cancer cell evolution,Lund University Research Groups
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- Lindell-Munther, Simon (author)
- Lund University
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- Yasui, Hiroaki (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Nagoya University
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- Jansson, Caroline (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancercellers evolution,Forskargrupper vid Lunds universitet,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Pathways of cancer cell evolution,Lund University Research Groups
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- Esfandyari, Javanshir (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Molecular Pediatric Oncology,Lund University Research Groups
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- Karlsson, Jenny (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancercellers evolution,Forskargrupper vid Lunds universitet,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Pathways of cancer cell evolution,Lund University Research Groups
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- Lau, Kimberly (author)
- Hospital for Sick Children, Toronto
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- Hui, Chi chung (author)
- University of Toronto,Hospital for Sick Children, Toronto
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- Bexell, Daniel (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Molecular Pediatric Oncology,Lund University Research Groups
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- Hopyan, Sevan (author)
- University of Toronto,Hospital for Sick Children, Toronto
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- Gisselsson, David (author)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancercellers evolution,Forskargrupper vid Lunds universitet,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Pathways of cancer cell evolution,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- 2018-11-29
- 2019
- English.
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In: Journal of Pathology. - : Wiley. - 0022-3417. ; 247:1
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Abstract
Subject headings
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- Wilms tumour is a paediatric malignancy with features of halted kidney development. Here, we demonstrate that the Iroquois homeobox genes IRX3 and IRX5 are essential for mammalian nephrogenesis and govern the differentiation of Wilms tumour. Knock-out Irx3−/Irx5− mice showed a strongly reduced embryonic nephron formation. In human foetal kidney and Wilms tumour, IRX5 expression was already activated in early proliferative blastema, whereas IRX3 protein levels peaked at tubular differentiation. Accordingly, an orthotopic xenograft mouse model of Wilms tumour showed that IRX3−/− cells formed bulky renal tumours dominated by immature mesenchyme and active canonical WNT/β-catenin-signalling. In contrast, IRX5−/− cells displayed activation of Hippo and non-canonical WNT-signalling and generated small tumours with abundant tubulogenesis. Our findings suggest that promotion of IRX3 signalling or inhibition of IRX5 signalling could be a route towards differentiation therapy for Wilms tumour, in which WNT5A is a candidate molecule for enforced tubular maturation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- differentiation
- Iroquois
- IRX3
- IRX5
- nephrogenesis
- Wilms tumour
- WNT5A
Publication and Content Type
- art (subject category)
- ref (subject category)
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Holmquist Mengel ...
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Lindell-Munther, ...
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Yasui, Hiroaki
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Jansson, Carolin ...
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Esfandyari, Java ...
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Karlsson, Jenny
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Lau, Kimberly
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Hui, Chi chung
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Bexell, Daniel
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Hopyan, Sevan
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Gisselsson, Davi ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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Journal of Patho ...
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Lund University