Cathy Tournier

Senior Lecturer

More than 1 in 3 people in the UK will develop some form of cancer during their lifetime. Fortunately, the overall survival of most cancer patients increased remarkably in the past decades through early detection, but also improved treatment protocols that include the surgical removal of tumour tissue and conventional chemotherapy and radiotherapy. However, the majority of these approaches are associated with severe side effects. Moreover, the prognosis for patients with relapsed and/or aggressive tumours remains extremely poor. Notably, most metastatic breast cancers that have spread to secondary sites are refractory to treatment and are therefore incurable. Thus, there is a pressing clinical need for further research to identify the basic mechanisms that drive cancer progression. Ultimately, this knowledge is essential to assist the design of future anti-cancer agents and improve the outcome of patients exhibiting aggressive clinical behaviour.

Cathy Tournier's University of Manchester research page

Email: Cathy.Tournier@manchester.ac.uk

Following the award of my PhD in 1996 from the University of Paris XI, France, I became a post-doctoral fellow in the laboratory of Professor Roger J Davis (University of Massachusetts, USA) where I discovered the power of combining molecular biology with mouse genetics to demonstrate the biological importance of mitogen-activated protein kinase (MAPK) signalling pathways. In July 2000, I was appointed as a lecturer in the Faculty of Life Sciences (now the Faculty of Biology, Medicine and Health) at the University of Manchester. A year later, I was awarded a Senior Research Fellowship from the Lister Institute of Preventive Medicine to focus on my research. In 2012, I was promoted to Senior Lecturer. The main interest of my group has remained in the scientific area of signal transduction via MAPKs. We are particularly interested in understanding the biological context in which these pathways operate.

Qualifications

• 1990: Bachelor (Licence) in Biochemistry, University of Montpellier, France
• 1991: Master (Maitrise) in Biochemistry, University of Montpellier, France
• 1996: PhD in Endocrinology and Cellular and Molecular Interactions, University of Paris XI, France

Memberships of committees and professional bodies

• Member of the scientific committee of Worldwide Cancer Research since 1/11/2015
• Editor of Biochemical Journal since May 2007
• Editorial board member of Molecular and Cellular biology journal since January 2010
• Associate Editor for Frontiers in Cell and Developmental Biology (specialty section: Signaling) since July 2020
• Member of the Advisory Panel of Essays in Biochemistry since April 2012

Xu Q, Zhang J, Telfer B, Zhang H, Ali N, Chen F, Risa B, Pearson AJ, Zhang W, Finegan KG, Ucar A, Giurisato E, Tournier C. (2021) The extracellular-regulated protein kinase 5 (ERK5) enhances metastatic burden in triple-negative breast cancer through focal adhesion protein kinase (FAK)-mediated regulation of cell adhesion. Oncogene 40, 3929-3941.

Giurisato E, Lonardi S, Telfer B, Lussoso S, Risa-Ebrí B, Zhang J, Russo I, Wang J, Santucci A, Finegan KG, Gray NS, Vermi W, Tournier C. (2020) Extracellular-regulated protein kinase 5-mediated control of p21 expression promotes macrophage proliferation associated with tumor growth and metastasis. Cancer Res 80, 3319-3330.

Pearson AJ, Fullwood P, Toro Tapia G, Prise I, Smith M, Xu Q, Jordan J, Giurisato E, Whitmarsh AJ, Francavilla C, Tournier C. (2020) Discovery of a gatekeeper residue in the C-terminal tail of the extracellular signal-regulated protein kinase 5 (ERK5). Int J Mol Sci 21, E929.

Giurisato E, Xu Q, Lonardi S, Telfer B, Russo I, Pearson A, Finegan KG, Wang W, Wang J, Gray NS, Vermi W, Xia Z, Tournier C. (2018) Myeloid ERK5 deficiency suppresses tumor growth by blocking protumor macrophage polarization via STAT3 inhibition. Proc Natl Acad Sci U S A. 115, E2801-E2810.

Gilbert AS, Seoane PI, Sephton-Clark P, Bojarczuk A, Hotham R, Giurisato E, Sarhan AR, Hillen A, Velde GV, Gray NS, Alessi DR, Cunningham DL, Tournier C, Johnston SA, May RC. (2017) Vomocytosis of live pathogens from macrophages is regulated by the atypical MAP kinase ERK5. Sci Adv. 3, e1700898.

Rovira-Clavé X, Angulo-Ibáñez M, Tournier C, Reina M, Espel E. (2016) Dual role of ERK5 in the regulation of T cell receptor expression at the T cell surface. J Leukoc Biol. 99, 143-52.

Wu L, Chen X, Zhao J, Martin B, Zepp JA, Ko JS, Gu C, Cai G, Ouyang W, Sen G, Stark GR, Su B, Vines CM, Tournier C, Hamilton TA, Vidimos A, Gastman B, Liu C, Li X. (2015) A novel IL-17 signaling pathway controlling keratinocyte proliferation and tumorigenesis via the TRAF4-ERK5 axis. J Exp Med. 212, 1571-87.

Finegan KG, Perez-Madrigal D, Hitchin JR, Davies CC, Jordan AM, Tournier C. (2015)^. ERK5 is a critical mediator of inflammation-driven cancer. Cancer Res. 75, 742-53.

The interest of my laboratory is to provide new scientific knowledge about the formation and progression of malignant tumours to advance the future development of rationale therapeutic strategies to combat metastatic cancer. This is achieved through studying how multiple cell types in tumours interact via the MAPK signalling network. In particular, we have found that the ERK5 MAPK stimulated the pathogenic activity of tumour-associated macrophages, also known as TAMs to promote tumour growth. Moreover, we have acquired initial molecular and cellular evidences that ERK5 signalling contributed to metastasis and therapeutic failure in breast cancer. Collectively, these data are clinically highly significant given that a high number of TAMs strongly associates with poor clinical outcome in a majority of patients with malignant solid tumours. Moreover, ERK5 has previously been linked to the pathophysiology of human breast cancer. We are currently exploring the therapeutic applicability of our discoveries using model organisms that reproduce the cellular heterogeneity observed in human tumours and credible computational modelling built using publicly available data from cancer patient materials.

Davies CC, Harvey E, McMahon RFT, Finegan KG, Connor F, Davis RJ, Tuveson DA, Tournier C. (2014) Impaired JNK signaling cooperates with Kras^G12D expression to accelerate pancreatic ductal adenocarcinoma. Cancer Res. 74, 3344-56.

Okamura D, Mochizuki K, Taniguchi H, Tokitake Y, Ikeda M, Yamada Y, Tournier C, Yamaguchi S, Tada T, Scholer HR,  Matsui Y. (2012) REST and its downstream molecule Mek5 regulate survival of primordial germ cells. Dev Biol. 372, 190-202.

Perez-Madrigal D, Finegan KG, Paramo B, Tournier C. (2012) The extracellular-regulated protein kinase 5 (ERK5) promotes cell proliferation through the down-regulation of inhibitors of cyclin dependent protein kinases (CDKs). Cell Signal. 24, 2360-2368.

Hübner A, Mulholland DJ, Standen CL, Karasarides M, Cavanagh-Kyros J, Barrett T, Chi H, Greiner DL, Tournier C, Sawyers CL, Flavell RA, Wu H, Davis RJ. (2012) JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate. Proc Natl Acad Sci U S A. 109, 12046-12051.

Le NT, Takei Y, Shishido T, Woo CH, Chang E, Heo KS, Lee H, Lu Y, Morrell C, Oikawa M, McClain C, Wang X, Tournier C, Molina CA, Taunton J, Yan C, Fujiwara K, Patterson C, Yang J, Abe J. (2012) p90RSK targets the ERK5-CHIP ubiquitin E3 ligase activity in diabetic hearts and promotes cardiac apoptosis and dysfunction. Circ. Res. 110, 536-550.

Mazzitelli S, Xu P, Ferrer I, Davis RJ, Tournier C (2011) The loss of JNK activity prevents the amyloidogenic cleavage of APP and the formation of amyloid plaques in vivo. J. Neurosci. 31, 16969 –16976.

Ahn YH, Yang Y, Gibbons DL, Creighton CJ, Yang F, Wistuba II, Lin W, Thilaganathan N, Alvarez CA, Roybal J, Goldsmith EJ, Tournier C, Kurie JM (2011) Map2k4 functions as a tumor suppressor in lung adenocarcinoma and inhibits tumor cell invasion by decreasing PPARg2. Mol. Cell. Biol. 31, 4270-4285.

Iñesta-Vaquera FA, Campbell DG, Tournier C, Gómez N, Lizcano JM, Cuenda A (2010) Alternative ERK5 regulation by phosphorylation during the cell cycle. Cell Signal 22, 1829-1837.

Finegan KG, Tournier C (2010) The mitogen-activated protein kinase kinase 4 (MKK4) has a pro-oncogenic role in skin cancer. Cancer Res. 70, 5797-5806.

Finegan KG, Wang X, Lee E-J, Robinson AC, Tournier C (2009) Regulation of neuronal survival by the extracellular signal-regulated protein kinase 5. Cell Death Differ. 16, 674-683.

Wang X, Nadarajah B, Robinson AC, McColl BW, Jin JW, Dajas-Bailador F, Boot-Handford RP, Tournier C (2007) Targeted deletion of the mitogen-activated protein kinase kinase 4 gene in the nervous system causes severe brain developmental defects and premature death. Mol. Cell. Biol. 27, 7935-7946.

Wang X, Finegan KG, Robinson AC, Knowles L, Khosravi-Far R, Hinchliffe KA, Boot-Handford RP, Tournier C (2006) Activation of extracellular signal-regulated protein kinase 5 down-regulates FasL upon osmotic stress. Cell Death Differ. 13, 2099-2108.

Seyfried J, Wang X, Kharebava G, Tournier C (2005) A novel MAPK docking site in the N-terminus of MEK5a organizes the components of the ERK5 signaling pathway. Mol. Cell. Biol.  25, 9820-9828.