Owen Sansom

Summary

Affiliation: University of Glasgow
Country: UK

Publications

  1. doi request reprint C-Myc is a critical mediator of the phenotypes of Apc loss in the intestine
    Julie A Wilkins
    Beatson Insitute of Cancer Research, Garscube Estate, Swithback Road, Glasgow, United Kingdom
    Cancer Res 68:4963-6. 2008
  2. pmc B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver
    Karen R Reed
    School of Biosciences, University of Cardiff, Cardiff CF10 3AX, United Kingdom
    Proc Natl Acad Sci U S A 105:18919-23. 2008
  3. pmc ROS Production and NF-κB Activation Triggered by RAC1 Facilitate WNT-Driven Intestinal Stem Cell Proliferation and Colorectal Cancer Initiation
    Kevin B Myant
    Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK
    Cell Stem Cell 12:761-73. 2013
  4. pmc The pro-apoptotic K-Ras 4A proto-oncoprotein does not affect tumorigenesis in the ApcMin/+ mouse small intestine
    Charles E Patek
    Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK
    BMC Gastroenterol 8:24. 2008
  5. pmc A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine
    Karen R Reed
    Cardiff School of Biosciences, Cardiff University, Cardiff, CF10 3US, UK
    BMC Cancer 8:162. 2008
  6. pmc PPARdelta status and mismatch repair mediated neoplasia in the mouse intestine
    Karen R Reed
    Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF103US, UK
    BMC Cancer 6:113. 2006
  7. pmc Loss of Apc allows phenotypic manifestation of the transforming properties of an endogenous K-ras oncogene in vivo
    Owen J Sansom
    Beatson Institute for Cancer Research, Glasgow G61 1BD, United Kingdom
    Proc Natl Acad Sci U S A 103:14122-7. 2006
  8. ncbi request reprint Tissue-specific tumour suppression by APC
    Owen Sansom
    Beaton Institute of Cancer Research, Glasgow, Scotland, UK
    Adv Exp Med Biol 656:107-18. 2009
  9. ncbi request reprint Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the intestine
    Owen J Sansom
    School of Biosciences, University of Cardiff, Museum P O Box 911, Cardiff CF103US, Wales, United Kingdom
    J Biol Chem 280:28463-7. 2005
  10. ncbi request reprint Myc deletion rescues Apc deficiency in the small intestine
    Owen J Sansom
    The Beatson Institute, Garscube Estate, Glasgow G61 1BD, UK
    Nature 446:676-9. 2007

Collaborators

Detail Information

Publications44

  1. doi request reprint C-Myc is a critical mediator of the phenotypes of Apc loss in the intestine
    Julie A Wilkins
    Beatson Insitute of Cancer Research, Garscube Estate, Swithback Road, Glasgow, United Kingdom
    Cancer Res 68:4963-6. 2008
    ..The importance of investigating Apc and C-Myc gene function in the correct tissue context is also discussed...
  2. pmc B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver
    Karen R Reed
    School of Biosciences, University of Cardiff, Cardiff CF10 3AX, United Kingdom
    Proc Natl Acad Sci U S A 105:18919-23. 2008
    ....
  3. pmc ROS Production and NF-κB Activation Triggered by RAC1 Facilitate WNT-Driven Intestinal Stem Cell Proliferation and Colorectal Cancer Initiation
    Kevin B Myant
    Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK
    Cell Stem Cell 12:761-73. 2013
    ..Mechanistically, RAC1-driven ROS and NF-κB signaling mediate these processes. Together, these data highlight that ROS production and NF-κB activation triggered by RAC1 are critical events in CRC initiation...
  4. pmc The pro-apoptotic K-Ras 4A proto-oncoprotein does not affect tumorigenesis in the ApcMin/+ mouse small intestine
    Charles E Patek
    Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK
    BMC Gastroenterol 8:24. 2008
    ..By this means tumorigenesis in the small intestine was compared between ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmDelta4A/tmDelta4A mice that can, and cannot, express the K-ras 4A proto-oncoprotein respectively...
  5. pmc A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine
    Karen R Reed
    Cardiff School of Biosciences, Cardiff University, Cardiff, CF10 3US, UK
    BMC Cancer 8:162. 2008
    ..Although p53-dependent regulation of Wnt signalling activity is known to occur, the importance of these regulatory mechanisms during the early stages of intestinal neoplasia has not been demonstrated...
  6. pmc PPARdelta status and mismatch repair mediated neoplasia in the mouse intestine
    Karen R Reed
    Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF103US, UK
    BMC Cancer 6:113. 2006
    ..To further investigate the PPARdelta dependency of intestinal tumourigenesis, we have analysed the consequences of PPARdelta deficiency upon intestinal neoplasia occurring in mice with impaired mismatch DNA repair...
  7. pmc Loss of Apc allows phenotypic manifestation of the transforming properties of an endogenous K-ras oncogene in vivo
    Owen J Sansom
    Beatson Institute for Cancer Research, Glasgow G61 1BD, United Kingdom
    Proc Natl Acad Sci U S A 103:14122-7. 2006
    ..These data imply a window of opportunity for anti-K-ras therapies after tumor initiation in preventing tumor growth and invasion...
  8. ncbi request reprint Tissue-specific tumour suppression by APC
    Owen Sansom
    Beaton Institute of Cancer Research, Glasgow, Scotland, UK
    Adv Exp Med Biol 656:107-18. 2009
    ....
  9. ncbi request reprint Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the intestine
    Owen J Sansom
    School of Biosciences, University of Cardiff, Museum P O Box 911, Cardiff CF103US, Wales, United Kingdom
    J Biol Chem 280:28463-7. 2005
    ..Taken together, this argues that cyclin D1 up-regulation in intestinal neoplasia is important for tumor progression rather than initiation...
  10. ncbi request reprint Myc deletion rescues Apc deficiency in the small intestine
    Owen J Sansom
    The Beatson Institute, Garscube Estate, Glasgow G61 1BD, UK
    Nature 446:676-9. 2007
    ..Array analysis revealed that Myc is required for the majority of Wnt target gene activation following Apc loss. These data establish Myc as the critical mediator of the early stages of neoplasia following Apc loss...
  11. pmc Efficient Wnt mediated intestinal hyperproliferation requires the cyclin D2-CDK4/6 complex
    Kevin Myant
    The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK
    Cell Div 6:3. 2011
    ..It also argues that inhibition of this complex may be an effective chemopreventative strategy in CRC...
  12. ncbi request reprint PPARdelta status and Apc-mediated tumourigenesis in the mouse intestine
    Karen R Reed
    Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF103US, UK
    Oncogene 23:8992-6. 2004
    ..Our data suggest that PPARdelta is not directly regulated by beta-catenin, and that inhibition of PPARdelta activity is unlikely to be an appropriate strategy for the chemoprevention or chemotherapy of intestinal malignancies...
  13. pmc Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration
    Owen J Sansom
    School of Biosciences, University of Cardiff, Cardiff CF10 3US, Wales
    Genes Dev 18:1385-90. 2004
    ..Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting...
  14. pmc Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis
    Dina Dikovskaya
    Division of Cell and Developmental Biology, University of Dundee, Dundee DD1 5EH, Scotland, UK
    J Cell Biol 176:183-95. 2007
    ..We suggest that these defects amplify each other to increase the incidence of tetra- and polyploidy in early stages of tumorigenesis...
  15. pmc Cyclin D2-cyclin-dependent kinase 4/6 is required for efficient proliferation and tumorigenesis following Apc loss
    Alicia M Cole
    Beatson Institute of Cancer Research, Glasgow, United Kingdom School of Biosciences, Cardiff, United Kingdom
    Cancer Res 70:8149-58. 2010
    ....
  16. ncbi request reprint APC as a master regulator of intestinal homeostasis and transformation: from flies to vertebrates
    Julia Cordero
    The Beatson Institute for Cancer Research, Glasgow, UK
    Cell Cycle 8:2926-31. 2009
    ..Here we discuss the similarities and differences between these model organisms in regards to the role of Wnt signaling and APC in intestinal homeostasis and transformation...
  17. pmc Spatial regulation of RhoA activity during pancreatic cancer cell invasion driven by mutant p53
    Paul Timpson
    The Beatson Institute for Cancer Research, Garscube Estate, Glasgow, United Kingdom
    Cancer Res 71:747-57. 2011
    ....
  18. ncbi request reprint Deficiency of Mbd2 suppresses intestinal tumorigenesis
    Owen J Sansom
    Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, UK
    Nat Genet 34:145-7. 2003
    ..As Mbd2-deficient mice are viable and fertile, their resistance to intestinal cancer may be of therapeutic relevance...
  19. doi request reprint p53 mutation and loss have different effects on tumourigenesis in a novel mouse model of pleomorphic rhabdomyosarcoma
    Brendan Doyle
    Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK
    J Pathol 222:129-37. 2010
    ..These data demonstrate that mutant p53 can co-operate with activated, mutant KRas to influence tumourigenesis and metastatic potential, over and above simple loss of normal protein function...
  20. pmc Deficiency of SPARC suppresses intestinal tumorigenesis in APCMin/+ mice
    Owen J Sansom
    Beatson Institute of Cancer Research, Glasgow, Scotland, UK
    Gut 56:1410-4. 2007
    ..More recently, it has been shown to be upregulated in human gastric and colorectal cancer. We therefore wished to address the functional importance of SPARC upregulation to intestinal tumorigenesis in vivo...
  21. pmc Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling
    Gabrielle H Ashton
    The Beatson Institute for Cancer Research, Glasgow, UK
    Dev Cell 19:259-69. 2010
    ..Importantly, this work suggests that FAK inhibitors may suppress tumorigenesis in patients at high risk of developing colorectal cancer...
  22. doi request reprint Advances in mouse models of prostate cancer
    Imran Ahmad
    The Beatson Institute for Cancer Research, Glasgow, UK
    Expert Rev Mol Med 10:e16. 2008
    ..Compound mutational models will also develop further, with double and triple knock-in or knockout systems adding to our knowledge of the interaction between different signalling cascades...
  23. pmc LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrest
    Jennifer P Morton
    Beatson Institute for Cancer Research, Garscube Estate, Glasgow, UK
    Gastroenterology 139:586-97, 597.e1-6. 2010
    ..In this study, we aimed to investigate the impact of LKB1 down-regulation for pancreatic cancer in mouse and human and to elucidate the mechanism by which Lkb1 deregulation contributes to this disease...
  24. doi request reprint Dasatinib inhibits the development of metastases in a mouse model of pancreatic ductal adenocarcinoma
    Jennifer P Morton
    Beatson Institute for Cancer Research, Glasgow, United Kingdom
    Gastroenterology 139:292-303. 2010
    ..The aim of this study was to assess the importance of Src in human PDAC and to use a genetically engineered mouse model of PDAC to determine the effects of dasatinib on PDAC progression...
  25. ncbi request reprint Identification of potential biomarkers for measuring inhibition of Src kinase activity in colon cancer cells following treatment with dasatinib
    Alan Serrels
    The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow, G61 1BD, United Kingdom
    Mol Cancer Ther 5:3014-22. 2006
    ..Thus, peripheral blood mononuclear cells may provide a useful surrogate tissue for biomarker studies with dasatinib using inhibition of Src Tyr(419) and paxillin Tyr(118) phosphorylation as read-outs of Src activity...
  26. ncbi request reprint Apoptosis and mutation in the murine small intestine: loss of Mlh1- and Pms2-dependent apoptosis leads to increased mutation in vivo
    Owen J Sansom
    School of Biosciences, University of Cardiff, Museum Avenue, P O Box 911, Cardiff, Wales CF10 3US, UK
    DNA Repair (Amst) 2:1029-39. 2003
    ..However, when MMR does mediate apoptosis, perturbation of this response leads to long-term persistence of mutant cells in vivo...
  27. doi request reprint Mutant p53 drives invasion by promoting integrin recycling
    Patricia A J Muller
    The Beatson Institute for Cancer Research, Switchback Road, Bearsden, Glasgow G61 1BD, UK
    Cell 139:1327-41. 2009
    ..These findings open the possibility that blocking alpha5/beta1-integrin and/or the EGF receptor will have therapeutic benefit in mutant p53-expressing cancers...
  28. pmc Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer
    Jennifer P Morton
    Beatson Institute for Cancer Research, Glasgow G61 1BD, United Kingdom
    Proc Natl Acad Sci U S A 107:246-51. 2010
    ....
  29. ncbi request reprint The ability to engage enterocyte apoptosis does not predict long-term crypt survival in p53 and Msh2 deficient mice
    Owen J Sansom
    Cardiff School of Biosciences, University of Cardiff, CF10 3US, UK
    Oncogene 21:5934-9. 2002
    ..We conclude that loss of either p53 or Msh2 dependent apoptosis does not predict long-term crypt survival in vivo, however genetic status clearly can modulate survival for some agents such as cisplatin...
  30. ncbi request reprint MBD4 deficiency does not increase mutation or accelerate tumorigenesis in mice lacking MMR
    Owen J Sansom
    School of Biosciences, University of Cardiff, Museum Avenue, PO Box 911, Cardiff CF10 3US, UK
    Oncogene 23:5693-6. 2004
    ..Taken together, these findings show that nullizygosity or heterozygosity for Mbd4 does not affect MMR-dependent tumorigenesis...
  31. ncbi request reprint Brca2 deficiency in the murine small intestine sensitizes to p53-dependent apoptosis and leads to the spontaneous deletion of stem cells
    Trevor Hay
    School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, UK
    Oncogene 24:3842-6. 2005
    ..Furthermore, we show that Brca2 deficiency results in the spontaneous deletion of stem cells, thereby protecting the small intestine against tumorigenesis...
  32. pmc Deficiency of Mbd2 attenuates Wnt signaling
    Toby J Phesse
    Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, United Kingdom
    Mol Cell Biol 28:6094-103. 2008
    ..Furthermore, we show that Lect2 is capable of functioning as a Wnt pathway repressor. These results therefore provide a mechanistic basis for the epigenetic control of adenoma formation mediated through Mbd2...
  33. ncbi request reprint Inactivation of Apc perturbs mammary development, but only directly results in acanthoma in the context of Tcf-1 deficiency
    Ronald C J Gallagher
    Department of Biomedical Sciences, University of Edinburgh, Medical School, Teviot Place, Edinburgh EH8 9AG, UK
    Oncogene 21:6446-57. 2002
    ..However, additional deficiency of Tcf-1 completely blocks normal mammary development and results in acanthoma...
  34. ncbi request reprint Analyzing tumor suppressor activities in the murine small intestine
    Alan R Clarke
    Cardiff School of Biosciences, Cardiff University, Cardiff, CF10 3US, UK
    Oncol Res 13:333-7. 2003
    ..Finally, we have analyzed mice mutant for Mbd4 and show that this gene functions in vivo as a tumor suppressor...
  35. ncbi request reprint Efficient deletion of normal Brca2-deficient intestinal epithelium by poly(ADP-ribose) polymerase inhibition models potential prophylactic therapy
    Trevor Hay
    School of Bioscience, Cardiff University, Cardiff, United Kingdom
    Cancer Res 65:10145-8. 2005
    ....
  36. ncbi request reprint Apc deficiency predisposes to renal carcinoma in the mouse
    Owen J Sansom
    Cardiff School of Biosciences, Cardiff University, Wales CF10 3US, UK
    Oncogene 24:8205-10. 2005
    ..Compared to other murine models of kidney neoplasia, this represents particularly rapid onset of disease, and so implicates an important role for Apc in suppressing renal carcinoma...
  37. ncbi request reprint Aspirin activates the NF-kappaB signalling pathway and induces apoptosis in intestinal neoplasia in two in vivo models of human colorectal cancer
    Lesley A Stark
    Division of Oncology, School of Clinical and Molecular Medicine, University of Edinburgh, Colon Cancer Genetics Group, MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
    Carcinogenesis 28:968-76. 2007
    ..These data have considerable relevance to cancer prevention and therapy...
  38. pmc Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc
    Vanesa Muncan
    Hubrecht Laboratory, Nederlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Mol Cell Biol 26:8418-26. 2006
    ..c-Myc appears essential for crypt progenitor cells to provide the necessary biosynthetic capacity to successfully progress through the cell cycle...
  39. ncbi request reprint Mutations in Apc and p53 synergize to promote mammary neoplasia
    Valerie Meniel
    School of Biological Sciences, Cardiff University, Cardiff, United Kingdom
    Cancer Res 65:410-6. 2005
    ..We therefore show clear synergy between these two mutations in mammary gland neoplasia and present data to suggest that at least one mechanism for this acceleration is the p53-dependent loss of Apc-deficient cells...
  40. ncbi request reprint Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin
    Heather Ireland
    Department of Oncology, Cancer Research UK, Cambridge Institute of Medical Research, Wellcome Trust MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
    Gastroenterology 126:1236-46. 2004
    ....
  41. ncbi request reprint Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice
    Catherine B Millar
    Wellcome Trust Centre for Cell Biology, The King s Buildings, Edinburgh University, Edinburgh EH9 3JR, UK
    Science 297:403-5. 2002
    ..On a cancer-susceptible Apc(Min/+) background, Mbd4-/- mice showed accelerated tumor formation with CpG --> TpG mutations in the Apc gene. Thus MBD4 suppresses CpG mutability and tumorigenesis in vivo...
  42. ncbi request reprint Mutationally activated K-ras 4A and 4B both mediate lung carcinogenesis
    Charles E Patek
    Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Edinburgh, UK
    Exp Cell Res 314:1105-14. 2008
    ....
  43. ncbi request reprint Heterozygosity for p53 promotes microsatellite instability and tumorigenesis on a Msh2 deficient background
    Neil J Toft
    Department of Pathology, University Medical School, Teviot Place, Edinburgh EH8 9AG, UK
    Oncogene 21:6299-306. 2002
    ..Our results therefore demonstrate a dose sensitive role for p53 in the maintenance of genomic integrity at the nucleotide level...
  44. ncbi request reprint Mechanisms of disease: methyl-binding domain proteins as potential therapeutic targets in cancer
    Owen J Sansom
    Cardiff School of Biosciences, Cardiff University, Cardiff, UK
    Nat Clin Pract Oncol 4:305-15. 2007
    ..We review the recent work addressing this possibility, and discuss several of the MBD proteins as potentially excellent novel therapeutic targets...