Owen Sansom - Colorectal Cancer and Wnt Signalling

Introduction

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Colorectal cancer is the third most common cancer in the UK and the second most common cause of cancer mortality.

The focus of our group is to understand the early changes associated with intestinal neoplasia in order to identify both novel markers of the disease as well as new targets for therapy.

The key intestinal tumour suppressor is the Apc gene that is mutated in approximately 80% of sporadic cancers. Central to our work is the use of novel inducible models of intestinal tumorigenesis that allow us to study the functions of specific tumour suppressor genes.

Want to find out more about Professor Sansom's work?

Read about his 2009 Nature paper on the CRUK science blog and listen to him talking about bowel cancer stem cells.

Lab Report

Key Publications

Faller WJ, Jackson TJ, Knight JR, Ridgway RA, Jamieson T, Karim SA, Jones C, Radulescu S, Huels DJ, Myant KB, Dudek KM, Casey HA, Scopelliti A, Cordero JB, Vidal M, Pende M, Ryazanov AG, Sonenberg N, Meyuhas O, Hall MN, Bushell M, Willis AE, Sansom OJ. mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature, 5 Nov 2014 [Epub ahead of print] doi: 10.1038/nature13896

Myant KB, Cammareri P, McGhee EJ, Ridgway RA, Huels DJ, Cordero JB, Schwitalla S, Kalna G, Ogg EL, Athineos D, Timpson P, Vidal M, Murray GI, Greten FR, Anderson KI, Sansom OJ. ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation. Cell Stem Cell 12, 761-73, 2013 doi: 10.1016/j.stem.2013.04.006

Ashton GH, Morton JP, Myant K, Phesse TJ, Ridgway RA, Marsh V, Wilkins JA, Athineos D, Muncan V, Kemp R, Neufeld K, Clevers H, Brunton V, Winton DJ, Wang X, Sears RC, Clarke AR, Frame MC, Sansom OJ. Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling. Dev Cell 19: 259-69, 2010

Morton JP, Timpson P, Karim SA, Ridgway RA, Athineos D, Doyle B, Jamieson NB, Oien KA, Lowy AM, Brunton VG, Frame MC, Evans TR, Sansom OJ. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci USA 107: 246-51, 2010

Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457: 608-11, 2009

Sansom OJ, Meniel VS, Muncan V, Phesse TJ, Wilkins JA, Reed KR, Vass JK, Athineos DA, Clevers H, Clarke AR. c-Myc deletion rescues Apc deficiency in the small intestine. Nature 446: 676-9, 2007

Sansom OJ, Reed KR, Hayes AJ, Ireland H, Brinkmann H, Newton IP, Batlle E, Simon-Assmann P, Clevers H, Nathke IS, Clarke AR, Winton DJ. Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration. Genes Dev 18: 1385-90, 2004

Biography

Education and qualifications

2002: PhD, University of Edinburgh, Supervisors Alan Clarke and Andrew Wylie
1997: MRes, Biology, University of Manchester
1996: BSc, Genetics (First Class Honours), University of Nottingham

Appointments

2011-present Deputy Director, CRUK Beatson Institute
2005-present: Group Leader, CRUK Beatson Institute
2000-2005: Postdoctoral Fellow with Alan Clarke, University of Cardiff

Current committee membership

NC3Rs Student Panel
CRUK Programme Grants interviewer
CRUK Drug Discovery Panel
North West Cancer Research Panel
CRUK Pancreatic Cancer Strategy Panel
Advisory Board, MRC Toxicology Unit, Leicester
Advisory Board, Center for Personalized Cancer Therapeutics, Mount Sinai
Advisory Board, Centre of Excellence in Translational Cancer Biology, Academy of Finland
Editorial Board, Disease Models and Mechanisms
Organising Committee, NCRI Cancer Conference, Liverpool

Honours and awards

CRUK Future Leaders in Cancer Research Prize, 2012
Fellow of the Royal Society of Edinburgh, 2012
BACR/AstraZeneca Young Scientist Frank Rose Award, 2007

Recent Publications

2016

Ahmad I, Mui E, Galbraith L, Patel R, Tan EH, Salji M, Rust AG, Repiscak P, Hedley A, Markert E, Loveridge C, van der Weyden L, Edwards J, Sansom OJ, Adams DJ, Leung HY (2016) Sleeping Beauty screen reveals Pparg activation in metastatic prostate cancer. Proceedings of the National Academy of Sciences of the United States of America 113: 8290-5

Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V et al. (2016) Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531: 47-52

Birch J, Clarke CJ, Campbell AD, Campbell K, Mitchell L, Liko D, Kalna G, Strathdee D, Sansom OJ, Neilson M, Blyth K, Norman JC (2016) The initiator methionine tRNA drives cell migration and invasion leading to increased metastatic potential in melanoma. Biology open

Cammareri P, Rose AM, Vincent DF, Wang J, Nagano A, Libertini S, Ridgway RA, Athineos D, Coates PJ, McHugh A, Pourreyron C, Dayal JH, Larsson J, Weidlich S, Spender LC, Sapkota GP, Purdie KJ, Proby CM, Harwood CA, Leigh IM et al. (2016) Inactivation of TGFbeta receptors in stem cells drives cutaneous squamous cell carcinoma. Nature communications 7: 12493

Cheung EC, Lee P, Ceteci F, Nixon C, Blyth K, Sansom OJ, Vousden KH (2016) Opposing effects of TIGAR- and RAC1-derived ROS on Wnt-driven proliferation in the mouse intestine. Genes & development 30: 52-63

Elbediwy A, Vincent-Mistiaen ZI, Spencer-Dene B, Stone RK, Boeing S, Wculek SK, Cordero J, Tan EH, Ridgway R, Brunton VG, Sahai E, Gerhardt H, Behrens A, Malanchi I, Sansom OJ, Thompson BJ (2016) Integrin signalling regulates YAP and TAZ to control skin homeostasis. Development 143: 1674-87

Erami Z, Herrmann D, Warren SC, Nobis M, McGhee EJ, Lucas MC, Leung W, Reischmann N, Mrowinska A, Schwarz JP, Kadir S, Conway JR, Vennin C, Karim SA, Campbell AD, Gallego-Ortega D, Magenau A, Murphy KJ, Ridgway RA, Law AM et al. (2016) Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue. Cell reports 14: 152-67

Gao Y, Vincent DF, Davis AJ, Sansom OJ, Bartholin L, Li Q (2016) Constitutively active transforming growth factor beta receptor 1 in the mouse ovary promotes tumorigenesis. Oncotarget
Jackstadt R, Sansom OJ (2016) Mouse models of intestinal cancer. The Journal of pathology 238: 141-51

Koppens MA, Bounova G, Cornelissen-Steijger P, de Vries N, Sansom OJ, Wessels LF, van Lohuizen M (2016) Large variety in a panel of human colon cancer organoids in response to EZH2 inhibition. Oncotarget

Lesina M, Wormann SM, Morton J, Diakopoulos KN, Korneeva O, Wimmer M, Einwachter H, Sperveslage J, Demir IE, Kehl T, Saur D, Sipos B, Heikenwalder M, Steiner JM, Wang TC, Sansom OJ, Schmid RM, Algul H (2016) RelA regulates CXCL1/CXCR2-dependent oncogene-induced senescence in murine Kras-driven pancreatic carcinogenesis. The Journal of clinical investigation 126: 2919-32

Marusiak AA, Stephenson NL, Baik H, Trotter EW, Li Y, Blyth K, Mason S, Chapman P, Puto LA, Read JA, Brassington C, Pollard HK, Phillips C, Green I, Overman R, Collier M, Testoni E, Miller CJ, Hunter T,

Sansom OJ et al. (2016) Recurrent MLK4 Loss-of-Function Mutations Suppress JNK Signaling to Promote Colon Tumorigenesis. Cancer research 76: 724-35

Steele CW, Karim SA, Leach JD, Bailey P, Upstill-Goddard R, Rishi L, Foth M, Bryson S, McDaid K, Wilson Z, Eberlein C, Candido JB, Clarke M, Nixon C, Connelly J, Jamieson N, Carter CR, Balkwill F, Chang DK, Evans TR et al. (2016) CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. Cancer cell 29: 832-45

Wildenberg ME, Koelink PJ, Diederen K, Te Velde AA, Wolfkamp SC, Nuij VJ, Peppelenbosch MP, Nobis M, Sansom OJ, Anderson KI, van der Woude CJ, D'Haens GR, van den Brink GR (2016) The ATG16L1 risk allele associated with Crohn's disease results in a Rac1-dependent defect in dendritic cell migration that is corrected by thiopurines. Mucosal Immunol

2015

Boulter L, Guest RV, Kendall TJ, Wilson DH, Wojtacha D, Robson AJ, Ridgway RA, Samuel K, Van Rooijen N, Barry ST, Wigmore SJ, Sansom OJ, Forbes SJ. WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. J Clin Invest 125: 1269-85, 2015

Conde-Perez A, Gros G, Longvert C, Pedersen M, Petit V, Aktary Z, Viros A, Gesbert F, Delmas V, Rambow F, Bastian BC, Campbell AD, Colombo S, Puig I, Bellacosa A, Sansom O, Marais R, Van Kempen LC, Larue L. A caveolin-dependent and PI3K/AKT-independent role of PTEN in beta-catenin transcriptional activity. Nat Commun 6: 8093, 2015

Davis H, Irshad S, Bansal M, Rafferty H, Boitsova T, Bardella C, Jaeger E, Lewis A, Freeman-Mills L, Giner FC, Rodenas-Cuadrado P, Mallappa S, Clark S, Thomas H, Jeffery R, Poulsom R, Rodriguez-Justo M, Novelli M, Chetty R, Silver A, Sansom OJ, Greten FR, Wang LM, East JE, Tomlinson I, Leedham SJ. Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche. Nat Med 21: 62-70, 2015

Faller WJ, Jackson TJ, Knight JR, Ridgway RA, Jamieson T, Karim SA, Jones C, Radulescu S, Huels DJ, Myant KB, Dudek KM, Casey HA, Scopelliti A, Cordero JB, Vidal M, Pende M, Ryazanov AG, Sonenberg N, Meyuhas O, Hall MN, Bushell M, Willis AE, Sansom OJ. mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature 517: 497-500, 2015

Ferrari N, Riggio AI, Mason S, McDonald L, King A, Higgins T, Rosewell I, Neil JC, Smalley MJ, Sansom OJ, Morris J, Cameron ER, Blyth K. Runx2 contributes to the regenerative potential of the mammary epithelium. Sci Rep 5: 15658, 2015

Flanagan DJ, Phesse TJ, Barker N, Schwab RH, Amin N, Malaterre J, Stange DE, Nowell CJ, Currie SA, Saw JT, Beuchert E, Ramsay RG, Sansom OJ, Ernst M, Clevers H, Vincan E. Frizzled7 functions as a wnt receptor in intestinal epithelial lgr5(+) stem cells. Stem Cell Reports 4: 759-67, 2015

Huels DJ, Ridgway RA, Radulescu S, Leushacke M, Campbell AD, Biswas S, Leedham S, Serra S, Chetty R, Moreaux G, Parry L, Matthews J, Song F, Hedley A, Kalna G, Ceteci F, Reed KR, Meniel VS, Maguire A, Doyle B, Soderberg O, Barker N, Watson A, Larue L, Clarke AR, Sansom OJ. E-cadherin can limit the transforming properties of activating beta-catenin mutations. EMBO J 34: 2321-33, 2015

Kundu P, Genander M, Straat K, Classon J, Ridgway RA, Tan EH, Bjork J, Martling A, van Es J, Sansom OJ, Clevers H, Pettersson S, Frisen J. An EphB-Abl signaling pathway is associated with intestinal tumor initiation and growth. Sci Transl Med 7: 281ra44, 2015

Lindstrom NO, Lawrence ML, Burn SF, Johansson JA, Bakker ER, Ridgway RA, Chang CH, Karolak MJ, Oxburgh L, Headon DJ, Sansom OJ, Smits R, Davies JA, Hohenstein P. Integrated beta-catenin, BMP, PTEN, and Notch signalling patterns the nephron. eLife 3: e04000, 2014

Lu WY, Bird TG, Boulter L, Tsuchiya A, Cole AM, Hay T, Guest RV, Wojtacha D, Man TY, Mackinnon A, Ridgway RA, Kendall T, Williams MJ, Jamieson T, Raven A, Hay DC, Iredale JP, Clarke AR, Sansom OJ, Forbes SJ. Hepatic progenitor cells of biliary origin with liver repopulation capacity. Nat Cell Biol 17: 971-83, 2015

Ma Y, Faller WJ, Sansom OJ, Brown ER, Doig TN, Melton DW, Machesky LM. Fascin expression is increased in metastatic lesions but does not correlate with progression nor outcome in melanoma. Melanoma Res  25: 169-72, 2014

Miller BW, Morton JP, Pinese M, Saturno G, Jamieson NB, McGhee E, Timpson P, Leach J, McGarry L, Shanks E, Bailey P, Chang D, Oien K, Karim S, Au A, Steele C, Carter CR, McKay C, Anderson K, Evans TR, Marais R, Springer C, Biankin A, Erler JT, Sansom OJ. Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy. EMBO Mol Med 7: 1063-76, 2015

Myant K, Qiao X, Halonen T, Come C, Laine A, Janghorban M, Partanen JI, Cassidy J, Ogg EL, Cammareri P, Laitera T, Okkeri J, Klefstrom J, Sears RC, Sansom OJ, Westermarck J. Serine 62-Phosphorylated MYC Associates with Nuclear Lamins and Its Regulation by CIP2A Is Essential for Regenerative Proliferation. Cell Rep 12: 1019-31, 2015

Steele CW, Karim SA, Foth M, Rishi L, Leach JD, Porter RJ, Nixon C, Jeffry Evans TR, Carter CR, Nibbs RJ, Sansom OJ, Morton JP. CXCR2 inhibition suppresses acute and chronic pancreatic inflammation in mice. J Pathol 237: 85-97, 2015

Topham C, Tighe A, Ly P, Bennett A, Sloss O, Nelson L, Ridgway RA, Huels D, Littler S, Schandl C, Sun Y, Bechi B, Procter DJ, Sansom OJ, Cleveland DW, Taylor SS. MYC Is a Major Determinant of Mitotic Cell Fate. Cancer Cell 28: 129-40, 2015

von Karstedt S, Conti A, Nobis M, Montinaro A, Hartwig T, Lemke J, Legler K, Annewanter F, Campbell AD, Taraborrelli L, Grosse-Wilde A, Coy JF, El-Bahrawy MA, Bergmann F, Koschny R, Werner J, Ganten TM, Schweiger T, Hoetzenecker K, Kenessey I, Hegedus B, Bergmann M, Hauser C, Egberts JH, Becker T, Rocken C, Kalthoff H, Trauzold A, Anderson KI, Sansom OJ, Walczak H. Cancer Cell-Autonomous TRAIL-R Signaling Promotes KRAS-Driven Cancer Progression, Invasion, and Metastasis. Cancer Cell 27: 561-73, 2015

Wiegering A, Uthe FW, Jamieson T, Ruoss Y, Huttenrauch M, Kuspert M, Pfann C, Nixon C, Herold S, Walz S, Taranets L, Germer CT, Rosenwald A, Sansom OJ, Eilers M. Targeting translation initiation bypasses signaling crosstalk mechanisms that maintain high MYC levels in colorectal cancer. Cancer Discov 5: 768-81, 2015

Gopinathan A, Morton JP, Jodrell DI, Sansom OJ. GEMMs as preclinical models for testing pancreatic cancer therapies. Dis Model Mech 8: 1185-200, 2015

Huels DJ, Sansom OJ. Stem vs non-stem cell origin of colorectal cancer. Br J Cancer 113: 1-5, 2015

Jackstadt R, Sansom OJ. Mouse models of intestinal cancer. J Pathol 2015. doi: 10.1002/path.4645. Epub 2015 Sep 28

Mills JC, Sansom OJ. Reserve stem cells: Differentiated cells reprogram to fuel repair, metaplasia, and neoplasia in the adult gastrointestinal tract. Sci Signal 8: re8, 2015

2014

Ali A, Brown V, Denley S, Jamieson NB, Morton JP, Nixon C, Graham JS, Sansom OJ, Carter CR, McKay CJ, Duthie FR, Oien KA. Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel. BMC Clin Pathol 2014; 14: 35

Arjonen A, Kaukonen R, Mattila E, Rouhi P, Hognas G, Sihto H, Miller BW, Morton JP, Bucher E, Taimen P, Virtakoivu R, Cao Y, Sansom OJ, Joensuu H, Ivaska J. Mutant p53-associated myosin-X upregulation promotes breast cancer invasion and metastasis. J Clin Invest 2014; 124: 1069-82

Belmont PJ, Budinska E, Jiang P, Sinnamon MJ, Coffee E, Roper J, Xie T, Rejto PA, Derkits S, Sansom OJ, Delorenzi M, Tejpar S, Hung KE, Martin ES. Cross-species analysis of genetically engineered mouse models of MAPK-driven colorectal cancer identifies hallmarks of the human disease. Dis Model Mech 2014; 7: 613-23

Cordero JB, Ridgway RA, Valeri N, Nixon C, Frame MC, Muller WJ, Vidal M, Sansom OJ. c-Src drives intestinal regeneration and transformation. EMBO J 2014; 33: 1474-91

Davis H, Irshad S, Bansal M, Rafferty H, Boitsova T, Bardella C, Jaeger E, Lewis A, Freeman-Mills L, Giner FC, Rodenas-Cuadrado P, Mallappa S, Clark S, Thomas H, Jeffery R, Poulsom R, Rodriguez-Justo M, Novelli M, Chetty R, Silver A, Sansom OJ, Greten FR, Wang LM, East JE, Tomlinson I, Leedham SJ. Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche. Nat Med 2015; 21: 62-70. doi: 10.1038/nm.3750. Epub 2014 Dec 1

Faller WJ, Jackson TJ, Knight JR, Ridgway RA, Jamieson T, Karim SA, Jones C, Radulescu S, Huels DJ, Myant KB, Dudek KM, Casey HA, Scopelliti A, Cordero JB, Vidal M, Pende M, Ryazanov AG, Sonenberg N, Meyuhas O, Hall MN, Bushell M, Willis AE, Sansom OJ. mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature 2015; 517: 497-500. doi: 10.1038/nature13896. Epub 2014 Nov 5

Foth M, Ahmad I, van Rhijn BW, van der Kwast T, Bergman AM, King L, Ridgway R, Leung HY, Fraser S, Sansom OJ, Iwata T. Fibroblast growth factor receptor 3 activation plays a causative role in urothelial cancer pathogenesis in cooperation with Pten loss in mice. J Pathol 2014; 233: 148-58

Hamilton G, Abraham AG, Morton J, Sampson O, Pefani DE, Khoronenkova S, Grawenda A, Papaspyropoulos A, Jamieson N, McKay C, Sansom O, Dianov GL, O'Neill E. AKT regulates NPM dependent ARF localization and p53mut stability in tumors. Oncotarget 2014; 5: 6142-67

Johnsson AK, Dai Y, Nobis M, Baker MJ, McGhee EJ, Walker S, Schwarz JP, Kadir S, Morton JP, Myant KB, Huels DJ, Segonds-Pichon A, Sansom OJ, Anderson KI, Timpson P, Welch HC. The Rac-FRET mouse reveals tight spatiotemporal control of Rac activity in primary cells and tissues. Cell Rep 2014; 6: 1153-64

Li A, Morton JP, Ma Y, Karim SA, Zhou Y, Faller WJ, Woodham EF, Morris HT, Stevenson RP, Juin A, Jamieson NB, MacKay CJ, Carter CR, Leung HY, Yamashiro S, Blyth K, Sansom OJ, Machesky LM. Fascin is regulated by slug, promotes progression of pancreatic cancer in mice, and is associated with patient outcomes. Gastroenterology 2014; 146: 1386-96 e1-17

Lindsay CR, Li A, Faller W, Ozanne B, Welch H, Machesky LM, Sansom OJ. A Rac1-independent role for P-Rex1 in melanoblasts. J Invest Dermatol 2015; 135: 314-8. doi: 10.1038/jid.2014.323. Epub 2014 Jul 30

Lunardi S, Jamieson NB, Lim SY, Griffiths KL, Carvalho-Gaspar M, Al-Assar O, Yameen S, Carter RC, McKay CJ, Spoletini G, D'Ugo S, Silva MA, Sansom OJ, Janssen KP, Muschel RJ, Brunner TB. IP-10/CXCL10 induction in human pancreatic cancer stroma influences lymphocytes recruitment and correlates with poor survival. Oncotarget 2014 ; 5: 11064-80

Meniel V, Megges M, Young MA, Cole A, Sansom OJ, Clarke AR. Apc and p53 interaction in DNA damage and genomic instability in hepatocytes. Oncogene 2014 Oct 27. doi: 10.1038/onc.2014.342. [Epub ahead of print]

Morran DC, Wu J, Jamieson NB, Mrowinska A, Kalna G, Karim SA, Au AY, Scarlett CJ, Chang DK, Pajak MZ, Oien KA, McKay CJ, Carter CR, Gillen G, Champion S, Pimlott SL, Anderson KI, Evans TR, Grimmond SM, Biankin AV, Sansom OJ, Morton JP. Targeting mTOR dependency in pancreatic cancer. Gut 2014; 63: 1481-9

Muinonen-Martin AJ, Susanto O, Zhang Q, Smethurst E, Faller WJ, Veltman DM, Kalna G, Lindsay C, Bennett DC, Sansom OJ, Herd R, Jones R, Machesky LM, Wakelam MJ, Knecht DA, Insall RH. Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal. PLoS Biol 2014; 12: e1001966

Peter S, Bultinck J, Myant K, Jaenicke LA, Walz S, Muller J, Gmachl M, Treu M, Boehmelt G, Ade CP, Schmitz W, Wiegering A, Otto C, Popov N, Sansom O, Kraut N, Eilers M. Tumor cell-specific inhibition of MYC function using small molecule inhibitors of the HUWE1 ubiquitin ligase. EMBO Mol Med 2014; 6: 1525-41

Phesse TJ, Myant KB, Cole AM, Ridgway RA, Pearson H, Muncan V, van den Brink GR, Vousden KH, Sears R, Vassilev LT, Clarke AR, Sansom OJ. Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo. Cell Death Differ 2014; 21: 956-66

Ragusa S, Cheng J, Ivanov KI, Zangger N, Ceteci F, Bernier-Latmani J, Milatos S, Joseph JM, Tercier S, Bouzourene H, Bosman FT, Letovanec I, Marra G, Gonzalez M, Cammareri P, Sansom OJ, Delorenzi M, Petrova TV. PROX1 promotes metabolic adaptation and fuels outgrowth of Wnt(high) metastatic colon cancer cells. Cell Rep 2014; 8: 1957-73

Rai TS, Cole JJ, Nelson DM, Dikovskaya D, Faller W, Vizioli MG, Hewitt RN, Anannya O, McBryan T, Manoharan I, van Tuyn J, Morrice N, Pchelintsev NA, Ivanov A, Brock C, Drotar M, Nixon C, Clark W, Sansom OJ, Anderson KI, King A, Blyth K, Adams PD. HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia. Genes Dev 2014; 28: 2712-25

Scopelliti A, Cordero JB, Diao F, Strathdee K, White BH, Sansom OJ, Vidal M. Local control of intestinal stem cell homeostasis by enteroendocrine cells in the adult Drosophila midgut. Curr Biol 2014; 24: 1199-211

Song JH, Huels DJ, Ridgway RA, Sansom OJ, Kholodenko BN, Kolch W, Cho KH. The APC network regulates the removal of mutated cells from colonic crypts. Cell Rep 2014; 7: 94-103

Ueberham E, Glockner P, Gohler C, Straub BK, Teupser D, Schonig K, Braeuning A, Hohn AK, Jerchow B, Birchmeier W, Gaunitz F, Arendt T, Sansom O, Gebhardt R, Ueberham U. Global increase of p16INK4a in APC-deficient mouse liver drives clonal growth of p16INK4a negative tumors. Mol Cancer Res 2015 F; 13: 239-49. doi: 10.1158/1541-7786.MCR-14-0278-T. Epub 2014 Sep 30

Valeri N, Braconi C, Gasparini P, Murgia C, Lampis A, Paulus-Hock V, Hart JR, Ueno L, Grivennikov SI, Lovat F, Paone A, Cascione L, Sumani KM, Veronese A, Fabbri M, Carasi S, Alder H, Lanza G, Gafa R, Moyer MP, Ridgway RA, Cordero J, Nuovo GJ, Frankel WL, Rugge M, Fassan M, Groden J, Vogt PK, Karin M, Sansom OJ, Croce CM. MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer. Cancer Cell 2014; 25: 469-83

Walz S, Lorenzin F, Morton J, Wiese KE, von Eyss B, Herold S, Rycak L, Dumay-Odelot H, Karim S, Bartkuhn M, Roels F, Wustefeld T, Fischer M, Teichmann M, Zender L, Wei CL, Sansom O, Wolf E, Eilers M. Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles. Nature 2014; 511: 483-7

Sansom O, Dhillon P. Translating the molecular hallmarks of colorectal cancer to patient therapies: an interview with Owen Sansom. Dis Model Mech 2014; 7: 937-40

2013

Huels DJ, Cammareri P, Ridgway RA, Medema JP, Sansom OJ. Methods to assess Myc function in intestinal homeostasis, regeneration, and tumorigenesis. Methods Mol Biol 1012: 237-48, 2013

Myant KB, Cammareri P, Cordero JB, McGhee EJ, Ridgway RA, Huels DJ, Schwitalla S, Kalna G, Ogg E, Athineos D, Timpson P, Vidal M, Murray GI, Greten FR, Anderson KI, Sansom OJ. Rac1 driven ROS production and NF-κB signalling is required for hyperproliferation, stemness and transformation following Apc loss. Cell Stem Cell 12: 761-73, 2013

Phesse TJ, Sansom OJ. Responding to R-spondin: slit2 potentiates intestinal regeneration. Cell Stem Cell 13: 512-4, 2013

Radulescu S, Ridgway RA, Cordero J, Athineos D, Salgueiro P, Poulsom R, Neumann J, Jung A, Patel S, Woodgett J, Barker N, Pritchard DM, Oien K, Sansom OJ. Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation. Oncogene 32(16): 2048-57, 2013

Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP, Athineos D, Kang TW, Lasitschka F, Andrulis M, Pascual G, Morris KJ, Khan S, Jin H, Dharmalingam G, Snijders AP, Carroll T, Capper D, Pritchard C, Inman GJ, Longerich T, Sansom OJ, Benitah SA, Zender L, Gil J. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 15: 978-90, 2013

Bird TG, Wie-YU L, Boulter L, Gordon-Keylock S, Ridgway RA, Williams MJ, Tauble J, Thomas J, Wojtacha D, Gambaardella A, Sansom OJ, Iredale JR, Forbes SJ. Bone marrow injections stimulate hepatic ductular reactions in the absence of injury via macrophage mediated TWEAK signalling. PNAS 110(16): 6542–7, 2013

Cheung E, Athineos D, Lee P, Ridgway R, Lambie W, Nixon C, Strathdee D, Blyth K, Sansom O, Vousden KH. TIGAR is required for efficient intestinal regeneration and tumorigensis. Dev Cell 25: 463-77, 2013

Guest RV, Boulter L, Kendall TJ, Minnis-Lyons SE, Walker R, Wigmore SJ, Sansom OJ, Forbes SJ. Cell lineage tracing reveals a biliary origin of intrahepatic cholangiocarcinoma. Cancer Res, in press 2013

Karim SA, Creedon H, Patel H, Carragher NO, Morton JP, Muller WJ, Evans TRJ, Gusterson B, OJ Sansom OJ, Brunton VG. Dasatinib inhibits mammary tumour development in a genetically engineered mouse model. Journal of Pathology 230: 430-40, 2013

Laine A, Sihto H, Come C, Rosenfeldt MT, Zwolinska A, Niemela M, Khanna A, Chan EK, Kahari VM, Kellokumpu-Lehtinen PL, Sansom OJ, Evan GI, Junttila MR, Ryan KM, Marine JC, Joensuu H, Westermarck J. Senescence sensitivity of breast cancer cells is defined by positive feedback loop between CIP2A and E2F1. Cancer Discov 3: 182-97, 2013

Lourenço FC, Munro J, Brown J, Cordero J, Stefanatos R, Strathdee K, Orange C, Feller SM, Sansom OJ, Vidal M, Murray GI, Olson MF. Reduced LIMK2 expression in colorectal cancer reflects its role in limiting stem cell proliferation. Gut doi:10.1136/gutjnl-2012-303883, published online 12 Apr 2013

Ma Y, Li A, Faller WJ, Libertini S, Fiorito F, Gillespie DA, Sansom OJ, Yamashiro S, Machesky LM. Fascin 1 is transiently expressed in mouse melanoblasts during development and promotes migration and proliferation. Development 140: 2203-11, 2013

Morton JP, Sansom OJ. MYC-y mice: from tumour initiation to therapeutic targeting of endogenous MYC. Mol Oncol 7: 248-58, 2013

Muller PA, Trinidad AG, Timpson P, Morton JP, Zanivan S, van den Berghe PV, Nixon C, Karim SA, Caswell PT, Noll JE, Coffill CR, Lane DP, Sansom OJ, Neilsen PM, Norman JC, Vousden KH. Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion. Oncogene 32(10): 1252-65, 2013

Myant KB, Scopelliti A, Haque S, Vidal M, Sansom OJ, Cordero JB. Rac1 drives intestinal stem cell proliferation and regeneration. Cell Cycle 12: 2973-7, 2013

Nobis M, Carragher NO, McGhee EJ, Morton JP, Sansom OJ, Anderson KI, Timpson P. Advanced intravital subcellular imaging reveals vital three-dimensional signalling events driving cancer cell behaviour and drug responses in live tissue. FEBS J 280: 5177-97, 2013

Nobis M, McGhee EJ, Morton JP, Schwarz JP, Karim SA, Quinn J, Edward M, Campbell AD, McGarry LC, Evans TR, Brunton VG, Frame MC, Carragher NO, Wang Y, Sansom OJ, Timpson P, Anderson KI. Intravital FLIM-FRET imaging reveals dasatinib-induced spatial control of src in pancreatic cancer. Cancer Res 73: 4674-86, 2013

Patel R, Gao M, Ahmad I, Fleming J, Singh L, Rai T, McKie A, Seywright M, Barnetson R, Edwards J, Sansom O, Leung H. Sprouty2, PTEN and PP2A interact to regulate prostate cancer progression. J Clin Invest 123(3): 1157-75, 2013

Rajan P, Sudbery IM, Villasevil ME, Mui E, Fleming J, Davis M, Ahmad I, Edwards J, Sansom OJ, Sims D, Ponting CP, Heger A, McMenemin RM, Pedley ID, Leung HY. Next-generation Sequencing of Advanced Prostate Cancer Treated with Androgen-deprivation Therapy. Eur Urol, in press 2013

Rosenfeldt MT, O'Prey J, Morton JP, Nixon C, Mackay G, Mrowinska A, Au A, Rai TS, Zheng L, Ridgway R, Adams PD, Anderson KI, Gottlieb E, Sansom OJ, Ryan KM. p53 status determines the role of autophagy in pancreatic tumour development. Nature, in press 2013

Schwitalla S, Fingerle AA, Cammareri P, Nebelsiek T, Göktuna SI, Ziegler PK, Canli O, Heijmans J, Huels DJ, Moreaux G, Rupec RA, Gerhard M, Schmid R, Barker N, Clevers H, Lang R, Neumann J, Kirchner T, Taketo MM, van den Brink GR, Sansom OJ, Arkan MC, Greten FR. Intestinal Tumorigenesis Initiated by Dedifferentiation and Acquisition of Stem-Cell-like Properties. Cell 152(1-2): 25-38, 2013

Steele CW, Jamieson NB, Evans TR, McKay CJ, Sansom OJ, Morton JP, Carter CR. Exploiting inflammation for therapeutic gain in pancreatic cancer. Br J Cancer 108: 997-1003, 2013

Tan EH, Morton JP, Timpson P, Tucci P, Melino G, Flores ER, Sansom OJ, Vousden KH, Muller PA. Functions of TAp63 and p53 in restraining the development of metastatic cancer. Oncogene, in press 2013

Wiese KE, Walz S, von Eyss B, Wolf E, Athineos D, Sansom O, Eilers M. The Role of MIZ-1 in MYC-Dependent Tumorigenesis. Cold Spring Harb Perspect Med 3, 2013

2012

Cordero JB, Stefanatos RK, Scopelliti A, Vidal M*, Sansom OJ*. Inducible progenitor-derived Wingless regulates adult midgut regeneration in Drosophila. EMBO J 31(19): 3901-17, 2012 *corresponding authors

Cordero JB, Stefanatos RK, Myant, K, Vidal M, Sansom OJ. Non-autonomous Jak/Stat and EGFR signaling crosstalk mediate intestinal stem cell proliferation following Apc loss in the Drosophila adult midgut. Development 139(24): 4524-35, 2012

Jamieson T, Clarke M, Steele CW, Samuel MS, Neumann J, Jung A, Huels D, Olson MF, Das S, Nibbs RJ, Sansom OJ. Inhibition of CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis. J Clin. Invest. 122(9): 3127-44, 2012

Radulescu S, Brookes MJ, Salgueiro P, Ridgway RA, McGhee E, Anderson K, Ford SJ, Stones DH, Iqbal TH, Tselepis C, Sansom OJ. Luminal iron levels govern intestinal tumorigenesis after apc loss in vivo. Cell Rep 2(2): 270-82, 2012v

Ridgway RA, Serrels B, Mason S, Kinnaird A, Muir M, Patel H, Muller WJ, Sansom OJ, Brunton VG. Focal adhesion kinase is required for beta-catenin-induced mobilization of epidermal stem cells. Carcinogenesis 33: 2369-76, 2012

Boulter L, Govaere O, Bird TG, Radulescu S, Ramachandran P, Pellicoro A, Ridgway RA, Seo SS, Spee B, Van Rooijen N, Sansom OJ, Iredale JP, Lowell S, Roskams T, Forbes SJ. Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nat Med 18: 572-9, 2012

Gao M, Patel R, Ahmad I, Fleming J, Edwards J, McCracken S, Sahadevan K, Seywright M, Norman J, Sansom O, Leung HY. SPRY2 loss enhances ErbB trafficking and PI3K/AKT signalling to drive human and mouse prostate carcinogenesis. EMBO Mol Med. 4(8): 776-90, 2012

Klotz DM, Nelson SA, Kroboth K, Newton IP, Radulescu S, Ridgway RA, Sansom OJ, Appleton PL, Nathke IS. The microtubule poison vinorelbine kills cells independently of mitotic arrest and targets cells lacking the APC tumour suppressor more effectively. J Cell Sci 125: 887-95, 2012

Li A, Ma Y, Jin M, Mason S, Mort RL, Blyth K, Larue L, Sansom OJ, Machesky LM. Activated Mutant NRas(Q61K) Drives Aberrant Melanocyte Signaling, Survival, and Invasiveness via a Rac1-Dependent Mechanism. J Invest Dermatol 132(11): 2610-21, 2012

McCall P, Bennett L, Ahmad I, Mackenzie LM, Forbes IW, Leung HY, Sansom OJ, Orange C, Seywright M, Underwood MA, Edwards J. NFkappaB signalling is upregulated in a subset of castrate-resistant prostate cancer patients and correlates with disease progression. Br J Cancer 107: 1554-63, 2012

Moyes LH, McEwan H, Radulescu S, Pawlikowski J, Lamm CG, Nixon C, Sansom OJ, Going JJ, Fullarton GM, Adams PD. Activation of Wnt Signalling promotes development of dysplasia in Barrett's Oesophagus. J Pathol 228(1): 99-112, 2012

Munoz J, Stange DE, Schepers AG, van de Wetering M, Koo BK, Itzkovitz S, Volckmann R, Kung KS, Koster J, Radulescu S, Myant K, Versteeg R, Sansom OJ, van Es JH, Barker N, van Oudenaarden A, Mohammed S, Heck AJ, Clevers H. The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent '+4' cell markers. EMBO J 31(14): 3079-91, 2012

Roth S, Franken P, Sacchetti A, Kremer A, Anderson K, Sansom O, Fodde R. Paneth cells in intestinal homeostasis and tissue injury. PLoS One 7: e38965, 2012

Blyth K, Morton JP, Sansom OJ. The right time, the right place: will targeting human cancer-associated mutations to the mouse provide the perfect preclinical model? Curr Opin Genet Dev 22: 28-35, 2012

Machesky LM, Sansom OJ. Rac1 in the driver's seat for melanoma. Pigment Cell Melanoma Res 25(6): 762-4, 2012

Tan EH, Sansom OJ. A new tumour suppressor enters the network of intestinal progenitor cell homeostasis. EMBO J 31: 2444-5, 2012v

Ahmad I, Sansom OJ, Leung HY. Exploring molecular genetics of bladder cancer: lessons learned from mouse models. Dis Model Mech 5: 323-32, 2012

2011

Ahmad I, Patel R, Liu Y, Singh LB, Taketo MM, Wu XR, Leung HY, Sansom OJ (2011). Ras mutation cooperates with beta-catenin activation to drive bladder tumourigenesis. Cell Death Dis. 2, e124.

Lindsay CR, Lawn S, Campbell AD, Faller WJ, Rambow F, Mort RL, Timpson P, Li A, Cammareri P, Ridgway RA, Morton JP, Doyle B, Hegarty S, Rafferty M, Murphy IG, McDermott EW, Sheahan K, Pedone K, Finn AJ, Groben PA, Thomas NE, Hao H, Carson C, Norman JC, Machesky LM, Gallagher WM, Jackson IJ, Van Kempen L, Beermann F, Der C, Larue L, Welch HC, Ozanne BW, Sansom OJ. P-Rex1 is required for efficient melanoblast migration and melanoma metastasis. Nat Commun doi: 10.1038/ncomms1560, published online 22 Nov 2011

Morton JP, Myant KB, Sansom OJ (2011). A FAK-PI-3K-mTOR axis is required for Wnt-Myc driven intestinal regeneration and tumorigenesis. Cell Cycle 10, 173-5.

Myant K, Sansom O (2011). Efficient Wnt mediated intestinal hyperproliferation requires the cyclin D2-CDK4/6 complex. Cell Div, 6, 3.

Ahmad I, Patel R, Singh LB, Nixon C, Seywright,M, Barnetson RJ, Brunton VG, Muller WJ, Edwards J, Sansom OJ, Leung HY. HER2 overcomes PTEN (loss)-induced senescence to cause aggressive prostate cancer. Proc Natl Acad Sci USA 2011; 108: 16392-7

Ahmad I, Singh LB, Foth M, Morris CA, Taketo MM, Wu XR, Leung HY, Sansom OJ, Iwata T (2011). K-Ras and beta-catenin mutations cooperate with Fgfr3 mutations in mice to promote tumorigenesis in the skin and lung, but not in the bladder. Dis Model Mech. 4, 548-55.

Dozynkiewicz MA, Jamieson NB, MacPherson I, Grindlay J, van den Berghe P, von Thun A, Morton JP, Gourley C, Timpson P, Nixon C, McKay CJ, Carter R, Strachan D, Anderson K, Sansom OJ, Caswell PT, Norman JC. Rab25 and CLIC3 collaborate to promote integrin recycling from late endosomes/lysosomes and drive cancer progression. Developmental Cell doi: 10.1016/j.devcel.2011.11.008, published online 22 Dec 2011

Graham K, Moran-Jones K, Sansom OJ, Brunton VG, Frame MC. FAK Deletion Promotes p53-Mediated Induction of p21, DNA-Damage Responses and Radio-Resistance in Advanced Squamous Cancer Cells. PLoS One 2011; 6: e27806

Jamieson NB, Morran DC, Morton JP, Ali A, Dickson EJ, Carter R, Sansom OJ, Evans T, McKay CJ, Oien KA. MicroRNA molecular profiles associated with diagnosis, clinicopathological criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinoma. Clin Cancer Res doi: 10.1158/1078- 0432.CCR-11-0679, published online 23 Nov 2011

Kennedy AL, Morton JP, Manoharan I, Nelson DM, Jamieson NB, Pawlikowski JS, McBryan T, Doyle B, McKay C, Oien KA, Enders GH, Zhang R, Sansom OJ, Adams PD (2011). Activation of the PIK3CA/AKT Pathway Suppresses Senescence Induced by an Activated RAS Oncogene to Promote Tumorigenesis. Mol Cell 42, 36-49.

Li A, Ma Y, Yu X, Mort RL, Lindsay CR, Stevenson D, Strathdee D, Insall RH, Chernoff J, Snapper SB, Jackson IJ, Larue L, Sansom OJ, Machesky LM. Rac1 Drives Melanoblast Organization during Mouse Development by Orchestrating Pseudopod- Driven Motility and Cell-Cycle Progression. Dev Cell 2011; 21: 722-34

Matallanas D, Romano D, Al-Mulla F, O’Neill E, Al- Ali W, Crespo P, Doyle B, Nixon C, Sansom O, Drosten M, Barbacid M, Kolch W. Mutant K-Ras activation of the proapoptotic MST2 pathway is antagonized by wildtype K-Ras. Mol Cell 2011; 44: 893-906

Matthews JR, Sansom OJ, Clarke AR (2011). Absolute requirement for STAT3 function in small-intestine crypt stem cell survival. Cell Death Differ. 2011 Jun 3. [Epub ahead of print].

Samuel MS, Lopez JI, McGhee EJ, Croft DR, Strachan D, Timpson P, Munro J, Schroder E, Zhou J, Brunton VG, Barker N, Clevers H, Sansom OJ, Anderson KI, Weaver VM, Olson MF (2011). Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth. Cancer Cell 19, 776-91.

Sandilands E, Serrels B, McEwan DG, Morton JP, Macgno JP, McLeod K, Stevens C, Brunton VG, Langdon WY, Vidal M, Sansom OJ, Dikic I, Wilkinson S, Frame MC. Autophagic targeting of SRC promotes cancer cell survival upon reduced FAK signalling. Nature Cell Biol doi:10.1038/ncb2386, published online 4 Dec 2011

Tho LM, Libertini S, Rampling R, Sansom O, Gillespie DA (2011). Chk1 is essential for chemical carcinogen-induced mouse skin tumorigenesis. Oncogene 2011 Aug 1. doi: 10.1038/onc.2011.326. [Epub ahead of print].

Timpson P, McGhee EJ, Morton JP, von Kriegsheim A, Schwarz JP, Karim SA, Doyle B, Quinn JA, Carragher NO, Edward M, Olson MF, Frame MC, Brunton VG, Sansom OJ, Anderson KI (2011). Spatial regulation of RhoA activity during pancreatic cancer cell invasion driven by mutant p53. Cancer Res. 71, 747-57.

Cordero JB, Sansom OJ (2011). Wnt signalling and its role in stem cell-driven intestinal regeneration and hyperplasia. Acta Physiol (Oxf). 2011 Mar 25. [Epub ahead of print].

Morton JP, Myant KB, Sansom OJ. A FAK-PI-3K-mTOR axis is required for Wnt-Myc driven intestinal regeneration and tumorigenesis. Cell Cycle 2011; 10: 173-5

Morton JP, Steele CW, Sansom OJ (2011). Timing is everything: Brca2 and p53 mutations in pancreatic cancer. Gastroenterology 140, 1143-6.

Myant K, Sansom O. Efficient Wnt mediated intestinal hyperproliferation requires the cyclin D2-CDK4/6 complex. Cell Div 2011; 6: 3

Myant K, Sansom OJ (2011). More, more, more: downregulation of a MK5-FoxO3a-mir34b/c pathway further increases c-Myc levels in colorectal cancer. Mol Cell 41, 369-70.

McGhee EJ, Morton JP, Von Kriegsheim A, Schwarz JP, Karim SA, Carragher NO, Sansom O, Anderson KI, Paul Timpson. FLIM-FRET imaging in vivo reveals 3D-environment spatially regulates RhoGTPase activity during cancer cell invasion. Small GTPases 2011; 2: 239-44

Images

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Lab Members

sansom lab 2013

Post-docs

Patrizia Cammareri (FP7)
Robert Fordham (1851 Royal Commission Research Fellow)
Rene Jackstadt (Marie Curie)
Joel Johansson
Arafath Kaja Najumudeen
John Knight
Dana Koludrovic (Marie Curie)
Karen Pickering (Novartis)
Chitra Subramani (Janssen)
David Vincent (ERC)

Scientific Officers

Andrew Campbell
Tam Jamieson
Emma Johnson
Rachel Ridgway

Clinical Research Fellow (Vet Path)

Joah Leach

PhD Students

David Gay (ERC)
Michael Hodder (MRC)

Research

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Read more about the Research Groups working at the Beatson Institute.

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Seminars

Beatson Institute Seminars

Find out more about our seminars including our Distinguished Seminar Programme.

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