A5019089933- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
- Lung Cancer Treatments and Mutations
- RNA Research and Splicing
- Cancer Cells and Metastasis
- Lung Cancer Research Studies
- Pancreatic and Hepatic Oncology Research
- Cancer-related molecular mechanisms research
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Single-cell and spatial transcriptomics
- Microtubule and mitosis dynamics
- Neuroendocrine Tumor Research Advances
- Acute Myeloid Leukemia Research
- Gene expression and cancer classification
- Cancer, Hypoxia, and Metabolism
- Genetic factors in colorectal cancer
- Immune Cell Function and Interaction
- Bioinformatics and Genomic Networks
- Zebrafish Biomedical Research Applications
- Ferroptosis and cancer prognosis
- Radiomics and Machine Learning in Medical Imaging
- Cancer Diagnosis and Treatment
AstraZeneca (United Kingdom)
2023-2024
National Cancer Centre Singapore
2014-2024
Cancer Research UK Manchester Institute
2005-2023
University of Manchester
2007-2023
Almac (United Kingdom)
2021
Cancer Research UK
2018
Addenbrooke's Hospital
2011
Karolinska Institutet
2011
Manchester Academic Health Science Centre
2011
University of Cambridge
2011
Abstract Small cell lung cancer (SCLC) is characterized by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin) cytokeratins consistent with vasculogenic mimicry (VM), a process whereby form ‘endothelial-like’ vessels. Single-cell genomic analysis reveals characteristic changes in both VE-cadherin-positive -negative CTCs. Higher levels of VM are...
Profiling tumors at single-cell resolution provides an opportunity to understand complexities underpinning lymph-node metastases in head and neck squamous-cell carcinoma. Single-cell RNAseq (scRNAseq) analysis of cancer-cell trajectories identifies a subpopulation pre-metastatic cells, driven by actionable pathways including AXL AURK. Blocking these two proteins blunts tumor invasion patient-derived cultures. Furthermore, scRNAseq analyses tumor-infiltrating CD8 + T-lymphocytes show distinct...
Chemo-resistance is one of the major causes cancer-related deaths. Here we used single-cell transcriptomics to investigate divergent modes chemo-resistance in tumor cells. We observed that higher degree phenotypic intra-tumor heterogeneity (ITH) favors selection pre-existing drug-resistant cells, whereas phenotypically homogeneous cells engage covert epigenetic mechanisms trans-differentiate under drug-selection. This adaptation was driven by selection-induced gain H3K27ac marks on...
Abstract Activation of p53 tumor suppressor induces either cell cycle arrest or apoptosis through transcription-dependent and independent pathways; however, their relative roles in induction how these pathways are regulated remains elusive. Here, we report a unique role for glycogen synthesis kinase-3β (GSK-3β) regulating functions human colorectal cancer cells. Pharmacologic modulation GSK-3β markedly impaired p53-dependent transactivation targets including p21 Puma but promoted...
Carcinoma of the oral tongue (OTSCC) is most common malignancy cavity, characterized by frequent recurrence and poor survival. The last three decades has witnessed a change in OTSCC epidemiological profile, with increasing incidence younger patients, females never-smokers. Here, we sought to characterize genomic landscape determine factors that may delineate genetic basis this disease, inform prognosis identify targets for therapeutic intervention. Seventy-eight cases were subjected...
Genomics-driven cancer therapeutics has gained prominence in personalized treatment. However, its utility indications lacking biomarker-driven treatment strategies remains limited. Here we present a "phenotype-driven precision-oncology" approach, based on the notion that biological response to perturbations, chemical or genetic, ex vivo patient-individualized models can serve as predictive biomarkers for therapeutic clinic. We generated library of "screenable" patient-derived primary...
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in world. The multikinase inhibitor sorafenib only demonstrated marginal improvement overall survival for advanced disease prompted search alternative treatment options. Human mesenchymal stem cells (MSCs) have ability to home tumor cells. However, its functional roles on microenvironment remain controversial. Herein, we showed that conditioned media derived from human fetal MSC (CM-hfMSCs) expressed high level...
(Cell 165, 910–920, May 5, 2016) Our paper demonstrated the cell-autonomous and non-cell-autonomous effects of oncogene signaling in tumor stromal cells using a proteomic approach. It has come to our attention that Data S1, which summarized phosphoproteomic data, included two sets errors. In tab related Figure 3E, data were labeled as representing log2-transformed ratios but erroneously formatted represent natural ratios. These numbers have now been changed copying error from proteomics...
Molecular information obtained from cancer patients' blood is an emerging and powerful research tool with immense potential as a companion diagnostic for patient stratification monitoring. Blood, which can be sampled routinely, provides means of inferring the current genetic status tumours via analysis circulating tumour cells (CTCs) or DNA (ctDNA). However, accurate assessment both CTCs ctDNA requires all to maintained intact until samples are processed. This dictates EDTA must processed 4...
SCLC accounts for approximately 250,000 deaths worldwide each year. Acquisition of adequate tumor biopsy samples is challenging, and liquid biopsies present an alternative option patient stratification response monitoring.
Abstract Non-coding RNAs (ncRNAs) are frequent and prevalent across the taxa. Although individual non-coding loci have been assigned a function, most uncharacterized. Their global biological significance is unproven remains controversial. Here we investigate role played by ncRNAs in stress response of Schizosaccharomyces pombe . We integrate proteomics RNA sequencing data to identify systematic programme which elevated antisense arising both from 3′-overlapping convergent gene pairs directly...
In NSCLC alterations in PDGF receptors are markers of worst prognosis and efficient targeting these is yet to be achieved. this study, we explored PDGFR-regulated microRNAs demonstrating that miR-23b cluster miR-125a-5p downregulated by increased expression PDGFR-α or PDGFR-β cells. Mechanistically, the positively regulated p53 negatively modulated NF-kB p65. Forced enhanced drug sensitivity suppressed invasiveness cells silencing several genes involved oncogenic KRAS pathways, including...
Abstract Oncogenic KRAS induces tumor onset and development by modulating gene expression via different molecular mechanisms. MicroRNAs (miRNAs) are small non-coding RNAs that have been established as main players in tumorigenesis. By overexpressing wild type or mutant (KRAS G12D ) using inducible human mouse cell lines, we analyzed KRAS-regulated microRNAs non-small-cell lung cancer (NSCLC). We show miR-30c miR-21 significantly upregulated both isoforms induce drug resistance enhance...
Abstract Serial biopsy of pancreatic ductal adenocarcinoma (PDAC), to chart tumour evolution presents a significant challenge. We examined the utility circulating free DNA (cfDNA) as minimally invasive approach across cohort 55 treatment-naïve patients with PDAC; 31 metastatic and 24 locally advanced disease. Somatic mutations in cfDNA were detected using next generation sequencing 15/24 (62.5%) 27/31 (87%) disease, respectively. Copy number changes 10 whom 7 exhibited gain chromosome 12p...
Abstract Wild-type KRAS ( WT ) amplification has been shown to be a secondary means of activation in cancer and associated with poor survival. Nevertheless, the precise role overexpression lung progression is largely unexplored. Here, we identify characterize KRAS-responsive lncRNA, KIMAT1 (ENSG00000228709) show that it correlates levels both cell lines specimens. Mechanistically, MYC target drives tumorigenesis by promoting processing oncogenic microRNAs (miRNAs) through DHX9 NPM1...
Treatment failure in solid tumors occurs due to the survival of specific subpopulations cells that possess tumor-initiating (TIC) phenotypes. Studies have implicated G protein-coupled-receptors (GPCRs) cancer progression and acquisition TIC Many GPCRs signal through protein GNA13. In this study, we demonstrate GNA13 is upregulated many impacts metastases patients. levels modulate drug resistance TIC-like phenotypes patient-derived head neck squamous cell carcinoma (HNSCC) vitro vivo....
The Core Binding Factor (CBF) protein RUNX1 is a master regulator of definitive hematopoiesis, crucial for hematopoietic stem cell (HSC) emergence during ontogeny. also plays vital roles in adult mice, regulating the correct specification numerous blood lineages. Akin to other mammalian Runx genes, Runx1 has two promoters P1 (distal) and P2 (proximal) which generate distinct isoforms. activities specific relevance these hematopoiesis remain be fully elucidated. Utilizing dual reporter mouse...