A5048548123- Immune cells in cancer
- Cell Adhesion Molecules Research
- Pancreatic and Hepatic Oncology Research
- Prostate Cancer Treatment and Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Radiomics and Machine Learning in Medical Imaging
- Phagocytosis and Immune Regulation
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Chemokine receptors and signaling
- Genetic factors in colorectal cancer
- Cancer-related gene regulation
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- Melanoma and MAPK Pathways
- Colorectal Cancer Treatments and Studies
- Protein Degradation and Inhibitors
- PARP inhibition in cancer therapy
- Cancer, Lipids, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Medical Imaging Techniques and Applications
- PI3K/AKT/mTOR signaling in cancer
- Epigenetics and DNA Methylation
Cancer Research UK
2015-2025
Weatherford College
2025
Disco (Germany)
2025
Cancer Research UK Scotland Institute
2015-2024
University of Glasgow
2004-2024
Switch
2022-2024
Glasgow Life
2012-2023
STCube (United States)
2012-2023
Imperial College London
2019
Harvard University
1997-2019
CXCR2 has been suggested to have both tumor-promoting and tumor-suppressive properties. Here we show that signaling is upregulated in human pancreatic cancer, predominantly neutrophil/myeloid-derived suppressor cells, but rarely tumor cells. Genetic ablation or inhibition of abrogated metastasis, only slowed tumorigenesis. Depletion neutrophils/myeloid-derived cells also suppressed metastasis suggesting a key role for establishing maintaining the metastatic niche. Importantly, loss improved...
The metastatic process of colorectal cancer (CRC) is not fully understood and effective therapies are lacking. We show that activation NOTCH1 signaling in the murine intestinal epithelium leads to highly penetrant metastasis (100% metastasis; with >80% liver metastases) Kras
Plasmax, a physiological cell culture medium, prevents metabolic artifacts imposed on cancer cells by commonly used media.
Here we show that Rab25 permits the sorting of ligand-occupied, active-conformation α5β1 integrin to late endosomes/lysosomes. Photoactivation and biochemical approaches lysosomally targeted integrins are not degraded but retrogradely transported recycled plasma membrane at back invading cells. This requires CLIC3, a protein upregulated in Rab25-expressing cells tumors, which colocalizes with active CLIC3 is necessary for release cell rear during migration on 3D matrices required invasion...
Abstract Pancreatic ductal adenocarcinoma (PDAC) develops a pronounced stromal response reflecting an aberrant wound-healing process. This reaction features transdifferentiation of tissue-resident pancreatic stellate cells (PSC) into activated cancer-associated fibroblasts, process induced by PDAC but unclear significance for progression. Here, we show that PSCs undergo dramatic lipid metabolic shift during differentiation in the context tumorigenesis, including remodeling intracellular...
Cellular senescence is a potent tumor suppressor mechanism but also contributes to aging and aging-related diseases. Senescence characterized by stable cell cycle arrest complex proinflammatory secretome, termed the senescence-associated secretory phenotype (SASP). We recently discovered that cytoplasmic chromatin fragments (CCFs), extruded from nucleus of senescent cells, trigger SASP through activation innate immunity cytosolic DNA sensing cGAS–STING pathway. However, upstream signaling...
Acetyl-CoA is a key metabolic intermediate with an important role in transcriptional regulation. The nuclear-cytosolic acetyl-CoA synthetase 2 (ACSS2) was found to sustain the growth of hypoxic tumor cells. It generates from acetate, but exactly which pathways it supports not fully understood. Here, quantitative analysis acetate metabolism reveals that ACSS2 fulfills distinct functions depending on its cellular location. Exogenous uptake controlled by expression both and mitochondrial ACSS1,...
Highlights•BRD4 represses a program of autophagy and lysosome genes independently MiT/TFE•BRD4 de-repression promotes certain types autophagy, but not others•Nutrient deprivation de-represses BRD4 via AMPK signaling to promote cell survival•Oncoprotein BRD4-NUT is potent repressor functionSummaryAutophagy membrane-trafficking process that directs degradation cytoplasmic material in lysosomes. The cellular fidelity, while the core machinery known, mechanisms sustain are less well defined....
Inhibiting acute injury–induced senescence mediated by TGFβ signaling in regenerative epithelium improves liver regeneration.
The TIGAR protein has antioxidant activity that supports intestinal tissue repair and adenoma development. Using a pancreatic ductal adenocarcinoma (PDAC) model, we show reactive oxygen species (ROS) regulation by premalignant tumor initiation while restricting metastasis. Increased ROS in PDAC cells drives phenotypic switch increases migration, invasion, metastatic capacity. This is dependent on increased activation of MAPK signaling can be reverted treatment. In mouse human, expression...
Pancreatic ductal adenocarcinoma (PDAC) is resistant to most therapies including single-agent immunotherapy and has a dense desmoplastic stroma, patients present with advanced metastatic disease. We reveal that macrophages are the dominant leukocyte population both in human PDAC stroma autochthonous models, an important functional contribution squamous subtype of PDAC. targeted genetic model using AZD7507, potent selective inhibitor CSF1R. AZD7507 caused shrinkage established tumors...
Article10 July 2017Open Access Source DataTransparent process Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium Steven E Reid Cancer Research UK Beatson Institute, Glasgow, Search for more papers by this author Emily J Kay Lisa Neilson Anne-Theres Henze Lab of Inflammation and Angiogenesis, Center Biology, VIB, Leuven, Belgium Jens Serneels Ewan McGhee Sandeep Dhayade Colin Nixon John BG Mackey Inflammation, Repair Development, Imperial College London,...
Abstract Despite the clinical success of Androgen Receptor (AR)-targeted therapies, reactivation AR signalling remains main driver castration-resistant prostate cancer (CRPC) progression. In this study, we perform a comprehensive unbiased characterisation LNCaP cells chronically exposed to multiple inhibitors (ARI). Combined proteomics and metabolomics analyses implicate an acquired metabolic phenotype common in ARI-resistant associated with perturbed glucose lipid metabolism. To exploit...
Abstract MYC is implicated in the development and progression of pancreatic cancer, yet precise level deregulation required to contribute tumor has been difficult define. We used modestly elevated expression human MYC, driven from Rosa26 locus, investigate phenotypes arising mice an approximation trisomy. show that this alone suffices drive neuroendocrine tumors, accelerate KRAS-initiated precursor lesions metastatic ductal adenocarcinoma (PDAC). Our phenotype exposed suppression type I...
Hepatocellular carcinoma (HCC) is increasingly associated with non-alcoholic steatohepatitis (NASH). HCC immunotherapy offers great promise; however, recent data suggests NASH-HCC may be less sensitive to conventional immune checkpoint inhibition (ICI). We hypothesised that targeting neutrophils using a CXCR2 small molecule inhibitor sensitise ICI therapy. Neutrophil infiltration was characterised in human and mouse models of HCC. Late-stage intervention anti-PD1 and/or performed murine...
Abstract Colorectal cancer (CRC) is a heterogenous malignancy underpinned by dysregulation of cellular signaling pathways. Previous literature has implicated aberrant JAK/STAT3 signal transduction in the development and progression solid tumors. In this study we investigate effectiveness inhibiting diverse CRC models, establish which contexts high pathway expression prognostic perform depth analysis underlying phenotypes. investigated use JAK inhibitors for anti-cancer activity cell lines,...
Tumour-derived mutant p53 proteins promote invasion, in part, by enhancing Rab coupling protein (RCP)-dependent receptor recycling. Here we identified MET as an RCP-binding and showed that promoted Mutant p53-expressing cells were more sensitive to hepatocyte growth factor, the ligand for MET, leading enhanced signalling, invasion cell scattering was dependent on both RCP. In expressing family member TAp63, inhibition of TAp63 also lead MET-dependent invasion. However, express very low...
Highlights•TIGAR is expressed in most adult tissue but dispensable for embryonic development•Intestinal damage induces TIGAR, which important gut regeneration•TIGAR provides reducing power and nucleotides rapid intestinal proliferation•TIGAR contributes to the development of tumors mice humansSummaryRegulation metabolic pathways plays an role controlling cell growth, proliferation, survival. TIGAR acts as a fructose-2,6-bisphosphatase, potentially promoting pentose phosphate pathway produce...
Metastasizing tumor cells use matrix metalloproteases, such as the transmembrane collagenase MT1-MMP, together with actin-based protrusions, to break through extracellular barriers and migrate in dense matrix. Here we show that actin nucleation–promoting protein N-WASP (Neural Wiskott-Aldrich syndrome protein) is up-regulated breast cancer, has a pivotal role mediating assembly of elongated pseudopodia are instrumental degradation. Although for invadopodia was known, now how regulates...