Owen Sansom

Summary

Affiliation: University of Glasgow
Country: UK

Publications

  1. Driscoll D, Karim S, Sano M, Gay D, Jacob W, Yu J, et al. mTORC2 Signaling Drives the Development and Progression of Pancreatic Cancer. Cancer Res. 2016;76:6911-6923 pubmed
    ..In late-stage tumor-bearing mice, combined mTORC1/2 and PI3K inhibition significantly increased survival. Thus, targeting mTOR may be a potential therapeutic strategy in pancreatic cancer. Cancer Res; 76(23); 6911-23. ©2016 AACR. ..
  2. Liko D, Mitchell L, Campbell K, Ridgway R, Jones C, Dudek K, et al. Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas. Cell Death Differ. 2019;: pubmed publisher
    ..However, Brf1 overexpression or heterozygosity are unable to modify tumorigenesis, suggesting a permissive, but not driving role for Brf1 in the development of epithelial cancers of the pancreas and gut. ..
  3. Johansson J, Nászai M, Hodder M, Pickering K, Miller B, Ridgway R, et al. RAL GTPases Drive Intestinal Stem Cell Function and Regeneration through Internalization of WNT Signalosomes. Cell Stem Cell. 2019;24:592-607.e7 pubmed publisher
    ..Together, we identify a conserved role for RAL GTPases in the promotion of optimal Wnt signaling, which defines ISC number and regenerative potential. ..
  4. Gay D, Ridgway R, Müller M, Hodder M, Hedley A, Clark W, et al. Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer. Nat Commun. 2019;10:723 pubmed publisher
    ..Importantly, loss of BCL9/9l is particularly effective at blocking colonic tumourigenesis and mutations that most resemble those that occur in human cancer. ..
  5. Hodder M, Flanagan D, Sansom O. Intestinal Stem Cell Dynamics: A Story of Mice and Humans. Cell Stem Cell. 2018;22:785-787 pubmed publisher
    ..2018) report that human intestinal stem cell dynamics differ significantly from those of mice and establish that oncogenic mutations are more likely to expand; therefore, "normal" epithelium may carry multiple mutations. ..
  6. Myant K, Sansom O. Efficient Wnt mediated intestinal hyperproliferation requires the cyclin D2-CDK4/6 complex. Cell Div. 2011;6:3 pubmed publisher
    ..It also argues that inhibition of this complex may be an effective chemopreventative strategy in CRC. ..
  7. Candido J, Morton J, Bailey P, Campbell A, Karim S, Jamieson T, et al. CSF1R+ Macrophages Sustain Pancreatic Tumor Growth through T Cell Suppression and Maintenance of Key Gene Programs that Define the Squamous Subtype. Cell Rep. 2018;23:1448-1460 pubmed publisher
    ..These changes were markedly different to those elicited when neutrophils were targeted via CXCR2. These results suggest targeting the myeloid cell axis may be particularly efficacious in PDAC, especially with CSF1R inhibitors. ..
  8. Huels D, Bruens L, Hodder M, Cammareri P, Campbell A, Ridgway R, et al. Wnt ligands influence tumour initiation by controlling the number of intestinal stem cells. Nat Commun. 2018;9:1132 pubmed publisher
    ..Therefore, ligand-based Wnt signalling influences the number of stem cells, fixation speed of Apc mutations and the speed and likelihood of adenoma formation. ..
  9. Huels D, Ridgway R, Radulescu S, Leushacke M, Campbell A, Biswas S, et al. E-cadherin can limit the transforming properties of activating β-catenin mutations. EMBO J. 2015;34:2321-33 pubmed publisher
    ..Thus, there is a threshold of β-catenin that is required to drive transformation, and E-cadherin can act as a buffer to sequester mutated β-catenin. ..

More Information

Publications20

  1. Leach J, Morton J, Sansom O. Neutrophils: Homing in on the myeloid mechanisms of metastasis. Mol Immunol. 2017;: pubmed publisher
    ..Neutrophils, however, have only recently emerged as important players, particularly in metastasis. Here we review the current evidence suggesting a multi-faceted role for neutrophils in the metastatic cascade. ..
  2. Steele C, Karim S, Leach J, Bailey P, Upstill Goddard R, Rishi L, et al. CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. Cancer Cell. 2016;29:832-845 pubmed publisher
    ..We show that CXCR2 signaling in the myeloid compartment can promote pancreatic tumorigenesis and is required for pancreatic cancer metastasis, making it an excellent therapeutic target. ..
  3. Patek C, Arends M, Rose L, Luo F, Walker M, Devenney P, et al. The pro-apoptotic K-Ras 4A proto-oncoprotein does not affect tumorigenesis in the ApcMin/+ mouse small intestine. BMC Gastroenterol. 2008;8:24 pubmed publisher
    ..The K-Ras 4A proto-oncoprotein does not exhibit tumour suppressor activity in the small intestine, even though the K-ras 4A/4B ratio is reduced in adenomas lacking K-ras activating mutations. ..
  4. Reed K, Sansom O, Hayes A, Gescher A, Peters J, Clarke A. PPARdelta status and mismatch repair mediated neoplasia in the mouse intestine. BMC Cancer. 2006;6:113 pubmed
    ..This data supports the notion that PPARdelta is not required for adenoma formation and indicate that any pro-tumourigenic effect of PPARdelta inactivation may be highly context dependent. ..
  5. request reprint
    Sansom O, Reed K, van de Wetering M, Muncan V, Winton D, Clevers H, et al. Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the intestine. J Biol Chem. 2005;280:28463-7 pubmed
    ..Taken together, this argues that cyclin D1 up-regulation in intestinal neoplasia is important for tumor progression rather than initiation. ..
  6. Huels D, Sansom O. R-spondin Is More Than Just Wnt's Sidekick. Dev Cell. 2017;41:456-458 pubmed publisher
    ..2017) show that Wnts and Wnt signaling potentiator R-spondins have non-interchangeable roles. Both are necessary for intestinal stem cell (ISC) maintenance, and R-spondins are the limiting factor that defines ISC number. ..
  7. Myant K, Qiao X, Halonen T, Come C, Laine A, Janghorban M, et al. Serine 62-Phosphorylated MYC Associates with Nuclear Lamins and Its Regulation by CIP2A Is Essential for Regenerative Proliferation. Cell Rep. 2015;12:1019-31 pubmed publisher
    ..These data underline the importance of nuclear organization in the regulation of MYC phosphorylation, leading to an in vivo demonstration of a strategy for inhibiting MYC activity without detrimental physiological effects. ..
  8. Lindsay C, Li A, Faller W, Ozanne B, Welch H, Machesky L, et al. A Rac1-independent role for P-Rex1 in melanoblasts. J Invest Dermatol. 2015;135:314-318 pubmed publisher
  9. Cordero J, Ridgway R, Valeri N, Nixon C, Frame M, Muller W, et al. c-Src drives intestinal regeneration and transformation. EMBO J. 2014;33:1474-91 pubmed publisher
    ..Therefore, we demonstrate a novel essential role for Src in intestinal stem/progenitor cell proliferation and tumourigenesis initiation in vivo. ..
  10. request reprint
    Sansom O, Meniel V, Muncan V, Phesse T, Wilkins J, Reed K, et al. Myc deletion rescues Apc deficiency in the small intestine. Nature. 2007;446:676-9 pubmed
    ..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. Sansom O, Meniel V, Wilkins J, Cole A, Oien K, Marsh V, et al. Loss of Apc allows phenotypic manifestation of the transforming properties of an endogenous K-ras oncogene in vivo. Proc Natl Acad Sci U S A. 2006;103:14122-7 pubmed
    ..These data imply a window of opportunity for anti-K-ras therapies after tumor initiation in preventing tumor growth and invasion. ..