The Wilms’ tumour suppressor Wt1 is a major regulator of tumour angiogenesis and progression

被引：0
作者：
Kay-Dietrich Wagner
Julien Cherfils-Vicini
Naoki Hosen
Peter Hohenstein
Eric Gilson
Nicholas D. Hastie
Jean-François Michiels
Nicole Wagner
机构：
[1] Institute for Research on Cancer and Aging,Division of Health Sciences
[2] Nice (IRCAN),Department of Medical Genetics
[3] Faculty of Medicine,Department of Pathology
[4] University of Nice Sophia-Antipolis,undefined
[5] Osaka University Graduate School of Medicine,undefined
[6] The Roslin Institute,undefined
[7] University of Edinburgh,undefined
[8] Easter Bush Campus,undefined
[9] Midlothian EH25 9RG,undefined
[10] UK,undefined
[11] CHU Nice,undefined
[12] MRC Human Genetics Unit,undefined
[13] MRC Institute of Genetics and Molecular Medicine,undefined
[14] University of Edinburgh,undefined
[15] CHU Nice,undefined
来源：
Nature Communications | / 5卷
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摘要：
Angiogenesis, activation of metastasis and avoidance of immune destruction are important for cancer progression. These biological capabilities are, apart from cancer cells, mediated by different cell types, including endothelial, haematopoietic progenitor and myeloid-derived suppressor cells. We show here that all these cell types frequently express the Wilms’ tumour suppressor Wt1, which transcriptionally controls expression of Pecam-1 (CD31) and c-kit (CD117). Inducible conditional knockout of Wt1 in endothelial, haematopoietic and myeloid-derived suppressor cells is sufficient to cause regression of tumour vascularization and an enhanced immune response, leading to decreased metastasis, regression of established tumours and enhanced survival. Thus, Wt1 is an important regulator of cancer growth via modulation of tumour vascularization, immune response and metastasis formation.
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[31]   Investigation of the role of Wilms' tumour suppressor gene 1 (WT1) isoforms in genito-urinary development [J].
Lahiri, D ;
Dutton, J ;
Ward, A .
GENETICAL RESEARCH, 2003, 81 (03) :240-240
[32]   Splicing of Exon 5 in the WT1 gene is disrupted in Wilms' tumour [J].
Simms, LA ;
Algar, EM ;
Smith, PJ .
EUROPEAN JOURNAL OF CANCER, 1995, 31A (13-14) :2270-2276
[33]   Loss of WT1 function leads to ectopic myogenesis in Wilms' tumour [J].
Kiyoshi Miyagawa ;
Jill Kent ;
Adrian Moore ;
Jean-Paul Charlieu ;
Melissa H. Little ;
Kathleen A. Williamson ;
Anna Kelsey ;
Keith W. Brown ;
Shabbir Hassam ;
Jakob Briner ;
Yasuhide Hayashi ;
Hisamaru Hirai ;
Yoshio Yazaki ;
Veronica van Heyningen ;
Nicholas D. Hastie .
Nature Genetics, 1998, 18 :15-17
[34]   Nuclear Transport of Wilms' Tumour Protein Wt1 Involves Importins α and β [J].
Depping, Reinhard ;
Schindler, Susann G. ;
Jacobi, Charlotte ;
Kirschner, Karin M. ;
Scholz, Holger .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2012, 29 (1-2) :223-232
[35]   Loss of WT1 function leads to ectopic myogenesis in Wilms' tumour [J].
Miyagawa, K ;
Kent, J ;
Moore, A ;
Charlieu, JP ;
Little, MH ;
Williamson, KA ;
Kelsey, A ;
Brown, KW ;
Hassam, S ;
Briner, J ;
Hayashi, Y ;
Hirai, H ;
Yazaki, Y ;
van Heyningen, V ;
Hastie, ND .
NATURE GENETICS, 1998, 18 (01) :15-17
[36]   Wilms' Tumour gene 1 (WT1) as an immunotherapeutic target in uterine cancer [J].
Coosemans, A. .
FACTS VIEWS AND VISION IN OBGYN, 2011, 3 (02) :89-99
[37]   Transcriptional regulation by the Wilms' tumour suppressor protein WT1. [J].
Addison, K ;
Boylan, K ;
Hartkamp, J ;
Green, L ;
Wagner, K ;
Roberts, S .
BRITISH JOURNAL OF CANCER, 2004, 91 :S7-S7
[38]   The ratio of ±KTS splice variants of the Wilms' tumour suppressor protein WT1 mRNA is determined by an intronic enhancer [J].
Yang, Cheng ;
Romaniuk, Paul J. .
BIOCHEMISTRY AND CELL BIOLOGY, 2008, 86 (04) :312-321
[39]   Role of the Wilms’ tumour transcription factor, Wt1, in blood vessel formation [J].
Holger Scholz ;
Kay-Dietrich Wagner ;
Nicole Wagner .
Pflügers Archiv - European Journal of Physiology, 2009, 458 :315-323
[40]   Loss of heterozygosity of WT1 gene in the prognosis of sporadic Wilms' tumour in children [J].
Skotnicka-Klonowicz, G ;
Rieske, P ;
Bartkowiak, J ;
Szymik-Kantorowicz, S ;
Daszkiewicz, P ;
Debiec-Rychter, M .
ANTICANCER RESEARCH, 1999, 19 (2B) :1451-1454
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