Prof Karen Blyth - In Vivo Cancer Biology

Introduction

blyth k

In vivo models are an important tool to recapitulate human cancer and interrogate aspects of the disease within a biological context. Validating in vitro discoveries in physiologically relevant models in this way will expedite novel therapeutic approaches for patient benefit. The group has expertise in modelling different cancer types but has a specific interest in breast cancer, and how metabolic pathways and certain signalling nodes such as the RUNX/CBFβ transcriptional complex and pro-survival factor MCL-1, contribute to tumour progression and metastasis.

The RUNX genes are essential regulators in mammalian development, most notably for bone and blood cell lineages. Like many genes important for normal development, the RUNX genes are linked to human cancer, but interestingly have been found to both promote and suppress tumour formation, a paradox we are exploring. We have shown that high expression of RUNX1 and RUNX2 in breast cancer correlates with specific subtypes of the disease and with poorer patient prognosis. We are now investigating the functionality of these genes in epithelial cancers and have shown that RUNX2 has a role in mammary stem/progenitor cells.


Other funding:

    BreastCancerNow 2020        

Lab Report

Key Publications

Blyth K, Carter P, Morrissey B, Chelala C, Jones L, Holen I and Speirs V. SEARCHBreast: a new resource to locate and share surplus archival material from breast cancer animal models to help address the 3Rs. Breast Cancer Res Treat. 2016; 56:447-52

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. Scientific Reports. 2015; 5:15658

Ferrari N, Mohammed ZMA, Nixon C, Mason SM, Mallon E, McMillan DC, Morris JS, Cameron ER, Blyth K. Expression of RUNX1 correlates with poor patient prognosis in triple negative breast cancer. PLOS One. 2014 9:e100759

McDonald L, Ferrari N, Terry A, Bell M, Mohammed ZM, Orange C, Jenkins A, Muller WJ, Gusterson BA, Neil JC, Edwards J, Morris JS, Cameron ER, Blyth K. RUNX2 correlates with subtype-specific breast cancer in a human tissue microarray and ectopic expression of Runx2 perturbs differentiation in the mouse mammary gland. Dis Model Mech. 2014 7:525-34

Blyth K, Vaillant F, Hanlon L, Mackay N, Bell M, Jenkins A, Neil JC, Cameron ER. Runx2 and MYC collaborate in lymphoma development by suppressing apoptotic and growth arrest pathways in vivo. Cancer Res. 2006; 66:2195-201

Blyth K, Cameron ER, Neil JC. The RUNX genes: gain or loss of function in cancer. Nat Rev Cancer. 2005; 5:376-87

Biography

Education and qualifications

1997: PhD, University of Glasgow, Supervisors Ewan Cameron & Moyra Campbell
1991: BSc, Biochemistry (Honours), University of Glasgow

Appointments

2009-present: Head of Transgenic Models, Cancer Research UK Beatson Institute, Glasgow
2009-present: Honorary Senior Lecturer, University of Glasgow
1997-2008: Postdoctoral Fellow, Molecular Oncology Lab, University of Glasgow
1991-1996: Research Assistant, University of Glasgow

Recent Publications

2020

Blagih J, Zani F, Chakravarty P, Hennequart M, Pilley S, Hobor S, Hock AK, Walton JB, Morton JP, Gronroos E, Mason S, Yang M, McNeish I, Swanton C, Blyth K, Vousden KH. Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses. Cell reports. 2020;30:481-496.e486.

Campbell KJ, Blyth K Somatic base editing to model oncogenic drivers in breast cancer Lab Anim. 2020; 49: 115–116

Caraffini V, Geiger O, Rosenberger A, Hatzl S, Perfler B, Berg JL, Lim C, Strobl H, Kashofer K, Schauer S, Beham-Schmid C, Hoefler G, Geissler K, Quehenberger F, Kolch W, Athineos D, Blyth K, Wolfler A, Sill H, Zebisch A. Loss of RAF kinase inhibitor protein is involved in myelomonocytic differentiation and aggravates RAS-driven myeloid leukemogenesis. Haematologica. 2020;

Cheung EC, DeNicola GM, Nixon C, Blyth K, Labuschagne CF, Tuveson DA, Vousden KH. Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer. Cancer cell. 2020; 37: 168-182

Dhayade S, Pietzke M, Wiesheu R, Tait-Mulder J, Athineos D, Sumpton D, Coffelt S, Blyth K, Vazquez A. Impact of Formate Supplementation on Body Weight and Plasma Amino Acids. Nutrients. 2020; 12(8):2181.

Dayal JHS, Mason SM, Salas-Alanis JC, McGrath JA, Taylor RG, Mellerio JE, Blyth K, South AP, Inman GJ. Heterogeneous addiction to TGFβ signalling in recessive dystrophic epidermolysis bullosa associated cutaneous squamous cell carcinoma. Br J Dermatol. 2020. [Online ahead of print]

Lie ALM, Mevel R, Patel R, Blyth K, Baena E, Kouskoff V, Lacaud G. RUNX1 Dosage in Development and Cancer. Mol Cells. 2020; 43: 126-128

Loveridge CJ, Slater S, Campbell KJ, Nam NA, Knight J, Ahmad I, Hedley A, Lilla S, Repiscak P, Patel R, Salji M, Fleming J, Mitchell L, Nixon C, Strathdee D, Neilson M, Ntala C, Bryson S, Zanivan S, Edwards J, Robson CN, Goodyear CS, Blyth K, Leung HY. BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration. Oncogene. 2020; 39: 1797–1806

MacKenzie DJ, Robertson NA, Rather I, Reid C, Sendzikaite G, Cruickshanks H, McBryan T, Hodges A, Pritchard C, Blyth K, Adams PD. DNMT3B Oncogenic Activity in Human Intestinal Cancer Is Not Linked to CIMP or BRAFV600E Mutation. iScience. 2020;23:100838-100838.

Millar R, Kilbey A, Remak SJ, Severson TM, Dhayade S, Sandilands E, Foster K, Bryant DM, Blyth K, Coffelt SB. The MSP-RON axis stimulates cancer cell growth in models of triple negative breast cancer. Molecular oncology. 2020;14: 1868-1880

Oizel K, Tait-Mulder J, Fernandez-de-Cossio-Diaz J, Pietzke M, Brunton H, Lilla S, Dhayade S, Athineos D, Blanco GR, Sumpton D, Mackay GM, Blyth K, Zanivan SR, Meiser J, Vazquez A. Formate induces a metabolic switch in nucleotide and energy metabolism. Cell death & disease. 2020;11:310.

Ran R, Harrison H, Syamimi Ariffin N, Ayub R, Pegg HJ, Deng W, Mastro A, Ottewell PD, Mason SM, Blyth K, Holen I, Shore P. A role for CBFbeta in maintaining the metastatic phenotype of breast cancer cells. Oncogene. 2020; 39: 2624–2637

Rooney N, Mason SM, McDonald L, Däbritz JHM, Campbell KJ, Hedley A, Howard S, Athineos D, Nixon C, Clark W, Leach JDG, Sansom OJ, Edwards J, Cameron ER, Blyth K RUNX1 is a driver of renal cell carcinoma correlating with clinical outcome Cancer Res. 2020;

Rudzka DA, Mason S, Neilson M, McGarry L, Kalna G, Hedley A, Blyth K, Olson MF. Selection of established tumour cells through narrow diameter micropores enriches for elevated Ras/Raf/MEK/ERK MAPK signalling and enhanced tumour growth. Small GTPases. 2020;10.1080/21541248.2020.1780108:1-17.

Sweeney K, Cameron ER, Blyth K. Complex Interplay between the RUNX Transcription Factors and Wnt/β-Catenin Pathway in Cancer: A Tango in the Night. Molecules and cells. 2020; 43: 188-197

Zhang T, Bauer C, Newman AC, Uribe AH, Athineos D, Blyth K, Maddocks ODK. Polyamine pathway activity promotes cysteine essentiality in cancer cells. Nature Metabolism. 2020.

2019

Hassan S, Purdie KJ, Wang J, Harwood CA, Proby CM, Pourreyron C, Mladkova N, Nagano A, Dhayade S, Athineos D, Caley M, Mannella V, Blyth K, Inman GJ, Leigh IM. A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing. International journal of molecular sciences. 2019; 20: 3428

Johnson SA, Ormsby MJ, McIntosh A, Tait SWG, Blyth K, Wall DM. Increasing the bactofection capacity of a mammalian expression vector by removal of the f1 ori. Cancer Gene Ther. 2019; 26: 183194

Liko D, Mitchell L, Campbell KJ, Ridgway RA, Jones C, Dudek K, King A, Bryson S, Stevenson D, Blyth K, Strathdee D, Morton JP, Bird TG, Knight JRP, Willis AE, Sansom OJ. Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas. Cell Death Differ. 2019; 26: 2535–2550

Rudzka DA, Spennati G, McGarry DJ, Chim YH, Neilson M, Ptak A, Munro J, Kalna G, Hedley A, Moralli D, Green C, Mason S, Blyth K, Mullin M, Yin H, Olson MF. Migration through physical constraints is enabled by MAPK-induced cell softening via actin cytoskeleton re-organization. Journal of cell science. 2019; 132:

Vande Voorde J, Ackermann T, Pfetzer N, Sumpton D, Mackay G, Kalna G, Nixon C, Blyth K, Gottlieb E, Tardito S. Improving the metabolic fidelity of cancer models with a physiological cell culture medium. Science Advances 2019; 5: eaau7314

2018

Campbell KJ, Dhayade S, Ferrari N, Sims AH, Johnson E, Mason SM, Dickson A, Ryan KM, Kalna G, Edwards J, Tait SWG, Blyth K. MCL-1 is a prognostic indicator and drug target in breast cancer. Cell Death Dis 2018; 9:19

McCarroll CS, He W, Foote K, Bradley A, McGlynn K, Vidler F, Nixon C, Nather K, Fattah C, Riddell A, Bowman P, Elliott EB, Bell M, Hawksby C, MacKenzie SM, et al. Runx1 Deficiency Protects Against Adverse Cardiac Remodeling After Myocardial Infarction. Circulation 2018; 137: 57-70.

Meiser J, Schuster A, Pietzke M, Vande Voorde J, Athineos D, Oizel K, Burgos-Barragan G, Wit N, Dhayade S, Morton JP, Dornier E, Sumpton D, Mackay GM, Blyth K, Patel KJ, et al. Increased formate overflow is a hallmark of oxidative cancer. Nat Commun. 2018; 9: 1368.

Novo D, Heath N, Mitchell L, Caligiuri G, MacFarlane A, Reijmer D, Charlton L, Knight J, Calka M, McGhee E, Dornier E, Sumpton D, Mason S, Echard A, Klinkert K, et al. Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels. Nat Commun 2018; 9: 5069.

2017

Bulusu V, Tumanov S, Michalopoulou E, van den Broek NJ, MacKay G, Nixon C, Dhayade S, Schug ZT, Vande Voorde J, Blyth K, Gottlieb E, Vazquez A, Kamphorst JJ. Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation. Cell Rep 2017; 18: 647-58

Dornier E, Rabas N, Mitchell L, Novo D, Dhayade S, Marco S, Mackay G, Sumpton D, Pallares M, Nixon C, Blyth K, Macpherson I, Rainero E, Norman JC. Glutaminolysis drives membrane trafficking to promote cancer invasion. Nat Commun 2017; 8: 2255.

Giampazolias E, Zunino B, Dhayade S, Bock F, Cloix C, Cao K, Roca A, Lopez J, Ichim G, Proics E, Rubio-Patino C, Fort L, Yatim N, Woodham E, Orozco S, Taraborrelli L, Peltzer N, Lecis D, Machesky L, Walczak H et al. Mitochondrial permeabilization engages NF-kappaB-dependent anti-tumour activity under caspase deficiency. Nat Cell Biol 2017; 19: 1116-29

Hernandez-Fernaud JR, Ruengeler E, Casazza A, Neilson LJ, Pulleine E, Santi A, Ismail S, Lilla S, Dhayade S, MacPherson IR, McNeish I, Ennis D, Ali H, Kugeratski FG, Al Khamici H, van den Biggelaar M, van den Berghe PV, Cloix C, McDonald L, Millan D et al. Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity. 2017 Nat Commun 8: 14206

Hock AK, Cheung EC, Humpton TJ, Monteverde T, Paulus-Hock V, Lee P, McGhee E, Scopelliti A, Murphy DJ, Strathdee D, Blyth K, Vousden KH. Development of an inducible mouse model of iRFP713 to track recombinase activity and tumour development in vivo. Sci Rep 2017; 7: 1837

Loveridge CJ, Mui EJ, Patel R, Tan EH, Ahmad I, Welsh M, Galbraith J, Hedley A, Nixon C, Blyth K, Sansom O, Leung HY. Increased T-cell Infiltration Elicited by Erk5 Deletion in a Pten-Deficient Mouse Model of Prostate Carcinogenesis. Cancer Res 2017; 77: 3158-68

Loveridge CJ, van 't Hof RJ, Charlesworth G, King A, Tan EH, Rose L, Daroszewska A, Prior A, Ahmad I, Welsh M, Mui EJ, Ford C, Salji M, Sansom O, Blyth K, Leung HY. Analysis of Nkx3.1:Cre-driven Erk5 deletion reveals a profound spinal deformity which is linked to increased osteoclast activity. Sci Rep 2017; 7: 13241

Maddocks ODK, Athineos D, Cheung EC, Lee P, Zhang T, van den Broek NJF, Mackay GM, Labuschagne CF, Gay D, Kruiswijk F, Blagih J, Vincent DF, Campbell KJ, Ceteci F, Sansom OJ, Blyth K, Vousden KH. Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature 2017; 544: 372-6

Reid SE, Kay EJ, Neilson LJ, Henze AT, Serneels J, McGhee EJ, Dhayade S, Nixon C, Mackey JB, Santi A, Swaminathan K, Athineos D, Papalazarou V, Patella F, Roman-Fernandez A, ElMaghloob Y, Hernandez-Fernaud JR, Adams RH, Ismail S, Bryant DM et al. Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO J 2017; 36: 2373-89

van Tuyn J, Jaber-Hijazi F, MacKenzie D, Cole JJ, Mann E, Pawlikowski JS, Singh Rai T, Nelson DM, McBryan T, Ivanov A, Blyth K, Wu H, Milling S, Adams PD. Oncogene-Expressing Senescent Melanocytes Upregulate Mhc Class Ii, A Candidate Melanoma Suppressor Function. J Invest Dermatol 2017; 137: 2197-207

Walton JB, Farquharson M, Mason S, Port J, Kruspig B, Dowson S, Stevenson D, Murphy D, Matzuk M, Kim J, Coffelt S, Blyth K, McNeish IA.
CRISPR/Cas9-derived models of ovarian high grade serous carcinoma targeting Brca1, Pten and Nf1, and correlation with platinum sensitivity. Sci Rep 2017;7: 16827

Weigert M, Binks A, Dowson S, Leung EYL, Athineos D, Yu X, Mullin M, Walton JB, Orange C, Ennis D, Blyth K, Tait SWG, McNeish IA. RIPK3 promotes adenovirus type 5 activity. Cell Death and Disease 2017; 8: 3206

Holen I, Speirs V, Morrissey B, Blyth K. In vivo models in breast cancer research: progress, challenges and future directions. Dis Model Mech 2017; 10: 359-71

Morrissey B, Blyth K, Carter P, Chelala C, Jones L, Holen I, Speirs V. The Sharing Experimental Animal Resources, Coordinating Holdings (SEARCH) Framework: Encouraging Reduction, Replacement, and Refinement in Animal Research. PLoS Biol 2017 15: e2000719

Riggio AI, Blyth K. The Enigmatic Role of RUNX1 in Female-Related Cancers: Current Knowledge & Future Perspectives. FEBS J 2017; 284: 2345-62

Rooney N, Riggio AI, Mendoza-Villanueva D, Shore P, Cameron ER, Blyth K. Runx Genes in Breast Cancer and the Mammary Lineage. Adv Exp Med Biol 2017; 962: 353-68

2016

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

Meiser J, Tumanov S, Maddocks O, Labuschagne CF, Athineos D, Van Den Broek N, Mackay GM, Gottlieb E, Blyth K, Vousden K, Kamphorst JJ, Vazquez A. Serine one-carbon catabolism with formate overflow. Science Advances 2: e1601273, 2016

Morrissey B, Blyth K, Carter P, Chelala C, Jones L, Holen I, Speirs V. SEARCHBreast: a new online resource to make surplus material from in vivo models of breast cancer visible and accessible to researchers. Breast Cancer Res 2016;18: 59.

Lab Members

Blyth lab 2020 52

Associate Scientist

Kirsteen J. Campbell

Scientific Officers

Jayanthi Anand
Dimitris Athineos
Laura Galbraith

PhD Students

Adiba Khan
Narisa Phinichkusolchit 
Kerri Sweeney (Breast Cancer Now)

 

Research

At the bench 3 160

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

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Seminars

Running a gel 154

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

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