Prof Jim Norman

Integrin Cell Biology

The microenvironment dictates how and where cancers originate and their spread throughout the body. The extracellular matrix (ECM) is an important component of the microenvironment and ECM components, such as fibronectin and collagen, are key to tumour initiation, growth and metastasis. Our laboratory is focussed on using mouse models to determine the molecular details of how the ECM influences initiation and metastasis of both liver and breast cancer and how the integrin receptors for the ECM control these processes in vivo. We report that integrin dependent deposition of fibronectin must occur early in tumorigenesis for cancers to propagate in the liver. Furthermore, we have found that, early in their development, breast tumours alter the metabolism of immune cells such as neutrophils to alter integrin behaviour. This leads to neutrophil recruitment to the lungs and subsequent metastasis to this organ. These studies highlight how drugs which target novel pathways controlling integrin function may be used to control both tumour initiation and metastasis.

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Biography

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Recent Publications

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Biography

Education and qualifications

1992: PhD, University of London
1985: BSc, Biochemistry, University of Southampton

Appointments

2009–present: Senior Group Leader, CRUK Scotland Institute
2005–2009: Junior Group Leader, CRUK Beatson Institute
2000–2005: Lecturer, Dept. Biochemistry, University of Leicester
1999–2004: Wellcome Career Development Fellow, Dept. Biochemistry, University of Leicester
1996–1998: Postdoctoral Fellow, Dept. Biochemistry, University of Leicester
1994–1996: Postdoctoral Fellow, Physiological Laboratory, University of Cambridge
1992–1994: Postdoctoral Fellow, Dept. Physiology, University College London

Honours and awards

Wellcome Trust Career Development Award, 1999-2004

Funding

Chief Scientist Office, MRC

Recent Publications

2026

Pardo L, Moore M, Deshmukh R, Powley I, Waldron JA, Kruspig B, McGarry L, Dolma L, Campos AV, Wood C, Leslie H, Hughes M, Jeldes E, Munro J, Mitchell L, Officer-Jones L, Baird R, Coquelet H, Jamieson NB, Sumpton D, Strathdee D, le Quesne J, Bushell M, Murphy DJ, Norman JC. Increased mRNA translation delays tumour initiation and exposes a therapeutic vulnerability in lung cancer. Mol Cancer. 2026.

2025

Gounis M, Campos AV, Shokry E, Mitchell L, Deshmukh R, Dornier E, Rooney N, Dhayade S, Pardo L, Moore M, Novo D, Mowat J, Jamieson C, Kay E, Zanivan S, Paul NR, Mitchell C, Nixon C, Macpherson I, Tardito S, Sumpton D, Blyth K, Norman JC, Clarke CJ. Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments. Journal of Cell Biology. 2025;224(8).

Marco S, Walsh PJ, Revenko AS, Thomason PA, McGarry L, MacLeod AR, Ansell S, Tataran D, Bushell M, Braconi C, Norman JC. EPHA2 and scavenger receptor-directed trafficking enhances endosomal leakiness and antisense therapy delivery. bioRxiv. 2025:2025.2002.2005.635637.

Whyte D, Fisher SL, McKenzie CGJ, Sumpton D, Dhayade S, Dornier E, Moore M, Novo D, Peters J, Wiesheu R, Gounis MD, Watt DM, Mackey JBG, McFarlane AJ, Fercoq F, Dehesa Caballero C, Redmond KL, Mitchell LE, Anderson E, Thomson G, Hedley A, Clark W, Leroi S, Dzierozynski LN, Apiz Saab JJ, Lewis CA, Muir A, Halbrook CJ, Strathdee D, Jackstadt R, Nixon C, Dunne P, Carlin LM, Macpherson IR, Roberts EW, Coffelt SB, Blyth K, Sansom OJ, Norman JC, Vande Voorde J, Clarke CJ. Uridine phosphorylase-1 supports metastasis by altering immune and extracellular matrix landscapes. EMBO Rep. 2025.

2024

Derby SJ, Dutton L, Strathdee KE, Stevenson K, Koessinger A, Jackson M, Tian Y, Yu W, McLay K, Misquitta J, Alsharif S, Clarke CJ, Gilmour L, Thomason P, McGhee E, McGarrity-Cottrell CL, Vanderlinden A, Collis SJ, Rominyi O, Lemgruber L, Solecki G, Olson M, Winkler F, Carlin LM, Heiland DH, Inman GJ, Chalmers AJ, Norman JC, Carruthers R, Birch JL. Inhibition of ATR opposes glioblastoma invasion through disruption of cytoskeletal networks and integrin internalization via macropinocytosis. Neuro Oncol. 2024;26(4):625-639.

Fercoq F, Cairns GS, Donatis MD, Mackey JBG, Floerchinger A, McFarlane A, Raffo-Iraolagoitia XL, Whyte D, Arnott LWG, Nixon C, Wiesheu R, Kilbey A, Brown L, Al-Khalidi S, Norman JC, Roberts EW, Blyth K, Coffelt SB, Carlin LM. Integrin inactivation slows down neutrophils congesting the pre-metastatic lung in a model of breast cancer. bioRxiv. 2024:2024.2003.2019.585724.

Fetit R, McLaren A, White M, Mills ML, Falconer J, Cortes-Lavaud X, Gilroy K, Lannagan TR, Ridgway RA, Nixon C, Naiker V, Njunge R, Clarke CJ, Whyte D, Kirschner K, Jackstadt R, Norman JC, Carlin LM, Campbell AD, Sansom OJ, Steele CW. Characterising neutrophil subtypes in cancer using scRNA sequencing demonstrates the importance of IL-1β/CXCR2 axis in generation of metastasis specific neutrophils. Cancer Res Commun. 2024.

Whyte D, Voorde JV, Sumpton D, Dhayade S, Dornier E, Moore M, Novo D, Peters J, Wiesheu R, Mackey JBG, McFarlane AJ, Fercoq F, Fisher S, Caballero CD, Gilroy K, Redmond KL, Mitchell LE, Anderson E, Thomson G, Dzierozynski LN, Saab JJA, Lewis CA, Muir A, Halbrook CJ, Strathdee D, Jackstadt R, Nixon C, Dunne P, Steele CW, Carlin LM, Macpherson IR, Roberts EW, Coffelt SB, Blyth K, Sansom OJ, Norman JC, Clarke CJ. Uridine Phosphorylase-1 supports metastasis of mammary cancer by altering immune and extracellular matrix landscapes of the lung. bioRxiv. 2024:2024.2007.2002.601676.

2023

Koessinger D, Novo D, Koessinger A, Campos A, Peters J, Dutton L, Paschke P, Zerbst D, Moore M, Mitchell L, Neilson M, Stevenson K, Chalmers A, Tait S, Birch J, Norman J. Glioblastoma extracellular vesicles influence glial cell hyaluronic acid deposition to promote invasiveness. Neuro-Oncology Advances. 2023;5:vdad067.

Moore M, Pardo L, Mitchell L, Schmidt T, May S, Mueller M, Strathdee D, Bryson S, Hodge K, Lilla S, Zanivan S, Waldron J, McGarry L, Peter-Durairaj R, Kanellos G, Nixon C, Ballantyne F, LeQuesne J, Sansom OJ, Bird T, Bushell M, Norman JC. The eIF4A2 negative regulator of mRNA translation promotes extracellular matrix deposition to accelerate hepatocellular carcinoma initiation. bioRxiv. 2023;Volume:2023.2008.2016.553544.

Nikolatou K, Sandilands E, Román-Fernández A, Cumming EM, Freckmann E, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant DM. PTEN deficiency exposes a requirement for an ARF GTPase module for integrin-dependent invasion in ovarian cancer. The EMBO Journal. 2023;n/a:e113987.

Román-Fernández A, Mansour MA, Kugeratski FG, Anand J, Sandilands E, Galbraith L, Rakovic K, Freckmann EC, Cumming EM, Park J, Nikolatou K, Lilla S, Shaw R, Strachan D, Mason S, Patel R, McGarry L, Katoch A, Campbell KJ, Nixon C, Miller CJ, Leung HY, Le Quesne J, Norman JC, Zanivan S, Blyth K, Bryant DM. Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function. Sci Adv. 2023;9:eabq1858.

Waldron JA, Kanellos G, Smith RCL, Knight JRP, Munro J, Alexandrou C, Vlahov N, Pardo-Fernandez L, Moore M, Gillen SL, Strathdee D, Stevenson D, Warrander FC, Gilroy K, Nixon C, Cadden B, Powley I, Officer-Jones L, Ballantyne F, Hay J, Pennel K, Edwards J, Campbell AD, Ridgway RA, Coffelt SB, Norman J, Quesne JL, Bushell M, Sansom OJ. eIF4A1 is essential for reprogramming the translational landscape of Wnt-driven colorectal cancers. bioRxiv. 2023:2023.2011.2010.566546.

Wilson B, Flett C, Gemperle J, Lawless C, Hartshorn M, Hinde E, Harrison T, Chastney M, Taylor S, Allen J, Norman JC, Zacharchenko T, Caswell P. Proximity labelling identifies pro-migratory endocytic recycling cargo and machinery of the Rab4 and Rab11 families. J Cell Sci. 2023;136:jcs260468.

2022

Jamshidiha M, Lanyon-Hogg T, Sutherell CL, Craven GB, Tersa M, De Vita E, Brustur D, Pérez-Dorado I, Hassan S, Petracca R, Morgan RM, Sanz-Hernández M, Norman JC, Armstrong A, Mann DJ, Cota E, Tate EW. Identification of the first structurally validated covalent ligands of the small GTPase RAB27A. RSC Med Chem. 2022;13:150-155.

Koessinger AL, Cloix C, Koessinger D, Heiland DH, Bock FJ, Strathdee K, Kinch K, Martínez-Escardó L, Paul NR, Nixon C, Malviya G, Jackson MR, Campbell KJ, Stevenson K, Davis S, Elmasry Y, Ahmed A, O’Prey J, Ichim G, Schnell O, Stewart W, Blyth K, Ryan KM, Chalmers AJ, Norman JC, Tait SWG. Increased apoptotic sensitivity of glioblastoma enables therapeutic targeting by BH3-mimetics. Cell Death & Differentiation. 2022;29:2089-2104.

Koessinger D, Novo D, Birch J, Mitchell L, Moore M, Zerbst D, Chalmers A, Koessinger A, Stevenson K, Nielson M, Norman JC. Glioblastoma exosomes influence glial cell hyaluronic acid deposition to promote invasiveness. bioRxiv. 2022.

Närvä E, Taskinen ME, Lilla S, Isomursu A, Pietilä M, Weltner J, Isola J, Sihto H, Joensuu H, Zanivan S, Norman J, Ivaska J. MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels. iScience. 2022;25:104459.

Nikolatou K, Sandilands E, Roman-Fernandez A, Cumming EM, Freckmann EC, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant D. PTEN deficiency exposes a requirement for an ARF GTPase module in integrin-dependent invasion in ovarian cancer. bioRxiv. 2022;Volume:2022.2011.2029.518198.

Rathan-Kumar S, Roland JT, Momoh M, Goldstein A, Lapierre LA, Manning E, Mitchell L, Norman J, Kaji I, Goldenring JR. Rab11FIP1-Deficient Mice Develop Spontaneous Inflammation and Show Increased Susceptibility to Colon Damage. Am J Physiol Gastrointest Liver Physiol. 2022;323:G239-G254.

2021

Mackey JBG, McFarlane AJ, Jamieson T, Jackstadt R, Raffo-Iraolagoitia XL, Secklehner J, Cortes-Lavaud X, Fercoq F, Clarke W, Hedley A, Gilroy K, Lilla S, Vuononvirta J, Graham GJ, De Filippo K, Murphy DJ, Steele CW, Norman JC, Bird TG, Mann DA, Morton JP, Zanivan S, Sansom OJ, Carlin LM. Maturation, developmental site, and pathology dictate murine neutrophil function. bioRxiv. 2021.

Marco S, Neilson M, Moore M, Perez-Garcia A, Hall H, Mitchell L, Lilla S, Blanco GR, Hedley A, Zanivan S, Norman JC. Nuclear-capture of endosomes depletes nuclear G-actin to promote SRF/MRTF activation and cancer cell invasion. Nat Commun. 2021;12(1):6829.

Nászai M, Bellec K, Yu Y, Román-Fernández A, Sandilands E, Johansson J, Campbell AD, Norman JC, Sansom OJ, Bryant DM, Cordero JB. RAL GTPases mediate EGFR-driven intestinal stem cell proliferation and tumourigenesis. Elife. 2021;10.

Phatak V, von Grabowiecki Y, Janus J, Officer L, Behan C, Aschauer L, Pinon L, Mackay H, Zanivan S, Norman JC, Kelly M, Le Quesne J, Muller PAJ. Mutant p53 promotes RCP-dependent chemoresistance coinciding with increased delivery of P-glycoprotein to the plasma membrane. Cell Death Dis. 2021;12(2):207.

Rabas N, Palmer S, Mitchell L, Ismail S, Gohlke A, Riley JS, Tait SWG, Gammage P, Soares LL, Macpherson IR, Norman JC. PINK1 drives production of mtDNA-containing extracellular vesicles to promote invasiveness. J Cell Biol. 2021;220:e202006049.

Jackstadt R, Norman JC. Stromal WNTer Keeps the Tumor Cold and Drives Metastasis. Dev Cell. 2021;56:3-4.

2020

Koessinger AL, Koessinger D, Stevenson K, Cloix C, Mitchell L, Nixon C, Gomez-Roman N, Chalmers AJ, Norman JC, Tait SWG. Quantitative in vivo bioluminescence imaging of orthotopic patient-derived glioblastoma xenografts. Scientific Reports. 2020;10(1):15361.

Sundararaman A, Fukushima Y, Norman JC, Uemura A, Mellor H. RhoJ Regulates α5β1 Integrin Trafficking to Control Fibronectin Remodeling during Angiogenesis. Current Biology. 2020;30:2146-2155.e5.

Taskinen ME, Närvä E, Conway JRW, Hinojosa LS, Lilla S, Mai A, De Franceschi N, Elo LL, Grosse R, Zanivan S, Norman JC, Ivaska J. MASTL promotes cell contractility and motility through kinase-independent signaling. J Cell Biol. 2020;219:e201906204.

2019

Auciello FR, Bulusu V, Oon C, Tait-Mulder J, Berry M, Bhattacharyya S, Tumanov S, Allen-Petersen BL, Link J, Kendsersky ND, Vringer E, Schug M, Novo D, Hwang RF, Evans RM, Nixon C, Dorrell C, Morton JP, Norman JC, Sears RC, Kamphorst JJ, Sherman MH. A stromal lysolipid-autotaxin signaling axis promotes pancreatic tumor progression. Cancer Discov. 2019;9:617-627.

Juin A, Spence HJ, Martin KJ, McGhee E, Neilson M, Cutiongco MFA, Gadegaard N, Mackay G, Fort L, Lilla S, Kalna G, Thomason P, Koh YWH, Norman JC, Insall RH, Machesky LM. N-WASP Control of LPAR1 Trafficking Establishes Response to Self-Generated LPA Gradients to Promote Pancreatic Cancer Cell Metastasis. Developmental Cell. 2019;51:431-445.

Linnane E, Davey P, Zhang P, Puri S, Edbrooke M, Chiarparin E, Revenko AS, Macleod AR, Norman JC, Ross SJ. Differential uptake, kinetics and mechanisms of intracellular trafficking of next-generation antisense oligonucleotides across human cancer cell lines. Nucleic Acids Res. 2019;47:4375-4392.

2018

Dornier E, Norman JC. Cancer cells with trapped nuclei cut their way through the extracellular matrix. Nat Commun 2018;9:3954.

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

Diaz-Vera J, Palmer S, Hernandez-Fernaud JR, Dornier E, Mitchell LE, MacPherson I, Edwards J, Zanivan S, Norman JC. A proteomic approach to identify endosomal cargoes controlling cancer invasiveness. J Cell Sci 2017;130:697-711.

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 Comms 2017;8:2255.

Gundry C, Marco S, Rainero E, Miller B, Dornier E, Mitchell L, Caswell PT, Campbell AD, Hogeweg A, Sansom OJ, Morton JP, Norman JC. Phosphorylation of Rab-coupling protein by LMTK3 controls Rab14-dependent EphA2 trafficking to promote cell:cell repulsion. Nat Commun 2017;8:14646.

Hall PS, Smith A, Hulme C, Vargas-Palacios A, Makris A, Hughes-Davies L, Dunn JA, Bartlett JMS, Cameron DA, Marshall A, Campbell A, Macpherson IR, Rea D, Francis A, Earl H, Morgan A, Stein RC, McCabe C, OPTIMA Trial Management Group. Value of information analysis of multiparameter tests for chemotherapy in early breast cancer: The OPTIMA Prelim Trial. Value Health 2017;20:1311-8.

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. Nat Commun 2017;8:14206.

Dornier E, Norman JC. Tensin links energy metabolism to extracellular matrix assembly. J Cell Biol 2017;216:867-9.

Norman J, Zanivan S. Chloride intracellular channel 3: A secreted pro-invasive oxidoreductase. Cell Cycle 2017;16:1993-4.

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. 2016;5:1371-9.

Boulay PL, Mitchell L, Turpin J, Huot-Marchand JE, Lavoie C, Sanguin-Gendreau V, Jones L, Mitra S, Livingstone JM, Campbell S, Hallett M, Mills GB, Park M, Chodosh L, Strathdee D, Norman JC, Muller WJ. Rab11-FIP1C is a critical negative regulator in ErbB2-mediated mammary tumor progression. Cancer Res. 2016;76:2662-74.

Clarke CJ, Berg TJ, Birch J, Ennis D, Mitchell L, Cloix C, Campbell A, Sumpton D, Nixon C, Campbell K, Bridgeman VL, Vermeulen PB, Foo S, Kostaras E, Jones JL, Haywood L, Pulleine E, Yin HB, Strathdee D, Sansom O, Blyth K, McNeish I, Zanivan S, Reynolds AR, Norman JC. The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis. Curr Biol. 2016;26:755-65.