A5090268906- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- Developmental Biology and Gene Regulation
- Epigenetics and DNA Methylation
- Adipose Tissue and Metabolism
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Signaling Pathways in Disease
- Cancer-related Molecular Pathways
- Pluripotent Stem Cells Research
- Wnt/β-catenin signaling in development and cancer
- 3D Printing in Biomedical Research
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
- Peptidase Inhibition and Analysis
- PI3K/AKT/mTOR signaling in cancer
- Virus-based gene therapy research
- Genomics, phytochemicals, and oxidative stress
- Autoimmune Neurological Disorders and Treatments
- Advanced Proteomics Techniques and Applications
- Pancreatic function and diabetes
- Genomics and Chromatin Dynamics
- Diet and metabolism studies
- Click Chemistry and Applications
University of Manchester
2014-2024
Cancer Research UK Manchester Institute
2010-2024
Medical University of South Carolina
2024
Sorbonne Université
2022
The Christie NHS Foundation Trust
2010-2020
Sahlgrenska University Hospital
2019
University of Gothenburg
2019
Breakthrough
2014
Breast Cancer Research Foundation
2014
University of Liverpool
2013
Notch receptor signaling pathways play an important role not only in normal breast development but also cancer and progression. We assessed the of receptors stem cell activity lines nine primary human tumor samples. Stem cells were enriched by selection anoikis-resistant or expressing membrane phenotype ESA(+)/CD44(+)/CD24(low). Using these populations, we compared activation status with luminally differentiated cells, evaluated consequences pathway inhibition vitro vivo. found that Notch4...
// Rebecca Lamb 1,2 , Hannah Harrison James Hulit Duncan L. Smith 3 Michael P. Lisanti and Federica Sotgia 1 The Manchester Centre for Cellular Metabolism (MCCM), Institute of Cancer Sciences, University 2 Breakthrough Breast Research Unit, UK Institute, Correspondence: Lisanti, email: Sotgia, Keywords : mitochondrial markers, cancer stem cells, proteomic analysis, ketone metabolism, monocarboxylate transporters (MCTs), AR-C155858, AZD3965, CHCHD2 Received November 02, 2014 Accepted 14,...
Abstract Introduction Although oestrogen is essential for the development of normal breast, adult mammary stem cells are known to be receptor alpha (ER) negative and rely on paracrine signals in epithelium mediation developmental cues. However, little about how systemic regulates breast cancer cell (CSC) activity. Methods Here, we tested effects CSC activity vitro vivo investigated which signalling pathways locally mediate effects. Results CSC-enriched populations (ESA + CD44 CD24 low )...
FK506-binding protein like (FKBPL) and its peptide derivative, AD-01, have already shown tumor growth inhibition CD44-dependent antiangiogenic activity. Here, we explore the ability of AD-01 to target CD44-positive breast cancer stem cells (BCSC).Mammosphere assays flow cytometry were used analyze effect FKBPL overexpression/knockdown treatment ± other anticancer agents on BCSCs using cell lines (MCF-7/MDA-231/ZR-75), primary patient samples, xenografts. Delays in initiation evaluated vivo....
// Rebecca Lamb 1,2 , Hannah Harrison Duncan L. Smith 3 Paul A. Townsend 1 Thomas Jackson Bela Ozsvari Ubaldo E. Martinez-Outschoorn 4 Richard G. Pestell Anthony Howell Michael P. Lisanti and Federica Sotgia The Manchester Centre for Cellular Metabolism (MCCM), Institute of Cancer Sciences, University Manchester, UK 2 Breakthrough Breast Research Unit, Institute, Kimmel Center, Philadelphia, PA, USA Correspondence: Lisanti, email: Sotgia, Keywords : tumor initiating cells, protein synthesis,...
Cancer progression is influenced by genetic aberrations in the cancer cell population as well other factors including microenvironment present within a tumour. Direct interactions between various types cellular signalling via secreted cytokines can drive key tumourigenic properties associated with disease and treatment resistance. Also, stem functions are microenvironment. This challenging subset of cells has been linked to malignant properties. Within screen, using vivo like growth...
Tumor hypoxia is often linked to decreased survival in patients with breast cancer and current therapeutic strategies aim target the hypoxic response. One way which this done by blocking hypoxia-induced angiogenesis. Antiangiogenic therapies show some potential increased disease-free survival, but these initial promising results are short lived followed tumor progression. We hypothesized that may be due altered stem cell (CSC) activity resulting from hypoxia. studied effects of on CSC...
The definitive characterization of common cancer stem cell (CSCs) subpopulations in breast subtypes with distinct genotypic and phenotypic features remains an ongoing challenge. In this study, we have used a non-biased genome wide screening approach to identify transcriptional networks that may be specific the CSC both luminal basal subtypes. depth studies three CSC-enriched lines representing various revealed striking hyperactivation mevalonate metabolic pathway comparison control cells....
The balance between self-renewal and differentiation of stem cells is expected to be tightly controlled in order maintain tissue homeostasis throughout life, also the face environmental hazards. Theory, predicting that maintained by a negative feedback on cell proliferation, implies Quorum Sensing mechanism higher vertebrates. Application this theory cellular automata model development disrupted environments shows sharply dichotomous growth dynamics: maturation within 50-400 cycles, or...
Hypoxia stimulates metastasis in cancer and is linked to poor patient prognosis. In tumours, oxygen levels vary hypoxic regions exist within a generally well-oxygenated tumour. However, whilst the heterogeneous environment known contribute metastatic progression, little about mechanism by which heterogeneic hypoxia contributes progression. This largely because existing experimental models do not recapitulate nature of hypoxia. The primary effector response transcription factor inducible...
Background Modulation of cellular signaling pathways can change the replication/differentiation balance in cancer stem cells (CSCs), thus affecting tumor growth and recurrence. Analysis a simple, experimentally verified, mathematical model suggests that this is maintained by quorum sensing (QS). Methodology/Principal Findings To explore mechanism which putative QS signals mammary (SCs) may regulate SC fate decisions, we developed multi-scale model, integrating extra-cellular intra-cellular...
It is well known that tumour cells are dependent on communication with the microenvironment. Previously, it has been shown hypoxia (HX) induces pronounced, diverse and direct effects cancer stem cell (CSC) qualities in different breast subtypes. Here, we describe mechanism by which HX-induced secretion influences spreading of CSCs. Conditioned media (CM) from estrogen receptor (ER)-α-positive hypoxic cultures increased fraction CSCs compared to normal growth conditions, as determined using...
// Hudhaifah Shaker 1 , Hannah Harrison 2 Robert Clarke 3 Goran Landberg 4 Nigel J. Bundred Henri H. Versteeg 5 and Cliona C. Kirwan The University of Manchester, Manchester Academic Health Science Centre, Department Surgery, Hospital South UK Faculty Life Sciences, Breast Biology Group, Cancer Research Sahlgrenska Center, Gothenburg, Sweden Thrombosis Hemostasis, Einthoven Laboratory for Experimental Vascular Medicine, Leiden Medical Leiden, Netherlands Correspondence to: Kirwan, email:...
Abstract Epithelial to mesenchymal transition (EMT) is a dynamic process that drives cancer cell plasticity and thought play major role in metastasis. Here we show, using MDA-MB-231 cells as model, the of at least some metastatic breast dependent on transcriptional co-regulator CBFβ. We demonstrate CBFβ essential maintain phenotype triple-negative CBFβ-depleted undergo epithelial (MET) re-organise into acini-like structures, reminiscent those formed by cells. subsequently an inducible...
Core binding factor β (CBFβ), the essential coregulator of RUNX transcription factors, is one most frequently mutated genes in estrogen receptor-positive (ER+) breast cancer. Many these mutations are nonsense and predicted to result loss function, suggesting a tumor suppressor role for CBFβ. However, impact missense CBFβ ER+ cancer cells have not been determined. Here we demonstrate that accumulate near Runt domain-binding region. These inhibit ability form CBFβ-Runx-DNA complexes. We...
Abstract Breast cancer remains a leading cause of mortality, predominantly due to the development metastases vital organs. At present, predictive biomarkers organ specific metastasis and therapies targeted metastatic niche are limited. Here, identify molecular determinants breast we analysed patient-derived tumours by combining quantitative proteomics, bioinformatics, functional assays in vitro vivo. We identified elevated levels protein Osteomodulin (OMD) associated with bone samples. OMD...