We are interested in how cancer cells interact with each other and the microenvironment. We investigate how cancer cell communication with neighbouring stromal cells and the extracellular matrix can impact on invasion and response to targeted therapies, to try to block cancer progression, with a particular focus on breast and pancreatic cancer.
Nuclear FGFR1 promotes pancreatic stellate cell-driven invasion through up-regulation of Neuregulin 1. Oncogene (2022). https://doi.org/10.1038/s41388-022-02513-5
FGF signalling facilitates cervical cancer progression. FEBS J (2021) 289(12):3440-3456. PMID: 34951738
PHLDA1 mediates drug resistance in receptor tyrosine kinase driven cancer. Cell Reports (2018) 22:1-13. PMID: 29490281
Pancreatic cancer cell invasion is mediated by nuclear translocation of FGFR1 and FGF2 in stellate cells. EMBO Mol Med (2014) 6:467-481. PMID: 24503018
FGFR1 cleavage and nuclear translocation regulates breast cancer cell behavior. Journal of Cell Biology. (2012) 197(6):801-17. PMID: 22665522
Receptor Tyrosine Kinase (RTK) signalling can be a positive driving force for cell proliferation, survival and migration but it is kept under tight control via feedback loops. In cancer, these controls can be bypassed by a variety of mechanisms and we are investigating how this happens.
We focus on breast and pancreatic cancer, using 2-D and 3-D cell-based models to investigate how cellular behaviour changes when cell signalling is altered. We collaborate with clinical colleagues to determine the translational significance of our findings through analysis of patient samples.
Our current research aims:
3D modelling fulfils a critical role in research, allowing for complex cell behaviour and interactions to be studied in physiomimetic conditions. We have used the Breast Cancer Now Tissue Bank, an invaluable resource of primary cells isolated directly from patients, to interrogate the interactions between myoepithelial and luminal cells in 3D using collagen gels. Using lentiviral transduction of isolated cells, we have developed a model that allows us to study early events in breast cancer development, to help understand how breast cancer progresses, with the ultimate aim of improving early diagnosis and treatment.
We have a number of projects investigating protease dependent activities, proteomic approaches to understanding cross-talk, impact of the innate immune system and RTK crosstalk with cannabinoid receptors.
Using advanced 3D cell based models we have identified a number of exciting new pathways implicated in stromal-led invasion in pancreatic cancer. We are investigating protease dependent activities, RTK-mediated pathways and purinergic signalling to identify novel biomarkers of disease progression and new targets for therapeutic intervention.
Fibroblast Growth Factor Receptor (FGFR) mutations are key drivers in a number of cancers, where dependency on oncogenic FGFR signalling makes FGFRs attractive targets for targeted therapies. We have worked extensively on endometrial, cervical breast and pancreatic cancer models, showing FGF signalling to play a critical role in cell migration and survival.
We have discovered that, rather than signalling from the cell surface or within endosomes, FGFRs can be proteolytically cleaved following activation and that the cytoplasmic portion of the receptor can traffic to the nucleus and regulate gene transcription. We have identified this behaviour in invasive breast cancer cells both in vitro and in vivo. We have shown that nuclear FGFR signalling is a critical mediator of cancer-stroma cross-talk in pancreatic cancer, and we are exploring the therapeutic potential of FGFR inhibition in blocking pancreatic cancer progression.
For more information, please visit www.groselab.com
Opposing roles for ADAMTS2 and ADAMTS14 in myofibroblast differentiation and function Carter E, Yoneten K, Gavara N et al. (2022) (18)
A 3d In Vitro Model To Unravel Myoepithelial-Macrophage Interactions In Breast Cancer Progression Roozitalab R, Allen M, Grose RP TISSUE ENGINEERING PART A (2022) 28(11) 113-113
Single-cell sequencing reveals the heterogeneity and intratumoral crosstalk in human endometrial cancer Yu Z, Zhang J, Zhang Q et al. Cell Proliferation (2022) 55(7)
Expression of programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand (PD-L1) in adenocarcinomas of the gastroesophageal junction change significantly after neoadjuvant treatment Jomrich G, Kollmann D, Ramazanova D et al. European Journal of Surgical Oncology (2022) 48(7) 383-390
Disruption of pancreatic stellate cell myofibroblast phenotype promotes pancreatic tumor invasion Murray ER, Menezes S, Henry JC et al. Cell Reports (2022) 38(7)
The Obscure Potential of AHNAK2. Zardab M, Stasinos K, Grose RP et al. Cancers (Basel) (2022) 14(2)
FGF signalling facilitates cervical cancer progression Mahmood HTNA, Tomas Bort E, Walker AJ et al. The Federation of European Biochemical Societies (FEBS) Journal (2022) (1)
Nuclear FGFR1 promotes pancreatic stellate cell-driven invasion through up-regulation of Neuregulin 1 Coetzee AS, Carter EP, Rodríguez-Fernández L et al. Oncogene (2022) (7)
Programmed death ligand 2 expression plays a limited role in adenocarcinomas of the gastroesophageal junction after preoperative chemotherapy Jomrich G, Kollmann D, Wilfing L et al. European Surgery - Acta Chirurgica Austriaca (2021) 53(7) 287-293
Biological significance and targeting of the fgfr axis in cancer Chioni AM, Grose RP Cancers (2021) 13(7)For additional publications, please click here