- S100 Proteins and Annexins
- Protease and Inhibitor Mechanisms
- Fungal and yeast genetics research
- Biomarkers in Disease Mechanisms
- Peptidase Inhibition and Analysis
- Thyroid Cancer Diagnosis and Treatment
- ATP Synthase and ATPases Research
- Protein Degradation and Inhibitors
- Computational Drug Discovery Methods
- Plant Disease Resistance and Genetics
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Radiopharmaceutical Chemistry and Applications
- Adenosine and Purinergic Signaling
- Polyamine Metabolism and Applications
- Endoplasmic Reticulum Stress and Disease
- Cellular Mechanics and Interactions
- Hydrogen embrittlement and corrosion behaviors in metals
- RNA Interference and Gene Delivery
- Biofuel production and bioconversion
- Neonatal Respiratory Health Research
- Plant-Microbe Interactions and Immunity
- Peroxisome Proliferator-Activated Receptors
- CRISPR and Genetic Engineering
University of Liverpool
2003-2023
University of Manchester
1999-2001
S100 proteins promote cancer cell migration and metastasis. To investigate their roles in the process of we have constructed inducible systems for S100P rat mammary human HeLa cells that show a linear relationship between its intracellular levels migration. S100P, like S100A4, differentially interacts with isoforms nonmuscle myosin II (NMIIA, Kd = 0.5 μm; IIB, 8 IIC, 1.0 μm). Accordingly, dissociates NMIIA IIC filaments but not IIB vitro. knockdown increases non-induced there is no further...
The ygdP and apaH genes of Salmonella enterica serovar Typhimurium (S. Typhimurium) encode two unrelated dinucleoside polyphosphate (Np n N) hydrolases. For example, YgdP cleaves diadenosine tetraphosphate (Ap4A) producing AMP ATP, while ApaH Ap4A 2ADP. Disruption ygdP, individually, disruption both together reduced intracellular invasion human HEp-2 epithelial cells by S. 9-, 250-, 3000-fold, respectively. Adhesion the mutants was also greatly compared with wild type. Invasive capacity...
Most patients who die of cancer do so from its metastasis to other organs. The calcium-binding protein S100A4 can induce cell migration/invasion and in experimental animals is overexpressed most human metastatic cancers. Here, we report that a novel inhibitor specifically block increase migration rat (IC50, 46 µM) (56 triple negative breast (TNBC) cells without affecting Western-blotted levels S100A4. moderately-weak S100A4-inhibitory compound, US-10113 has been chemically attached...
The calcium-binding protein S100A4 can induce a metastatic phenotype in animal model systems and its expression various human cancers has been shown to be associated with metastasis reduced patient survival. Using series of nested deletion mutants, it is now that the two C-terminal lysine residues are required for enhanced metastasis, invasion migration abilities confers on cells system metastasis. Basic enhance affinity between best characterized target, recombinant fragment non-muscle...
Elevated levels of the calcium-binding protein S100A4 promote metastasis and in carcinoma cells are associated with reduced survival cancer patients. interacts target proteins that affect a number activities metastatic cells. However, it is not known how many these interactions required for S100A4-promoted metastasis, thus hampering design specific inhibitors S100A4-induced metastasis. Intracellular exists as homodimer through previously identified, well conserved, predominantly hydrophobic...
Abstract Many human glandular cancers metastasize along nerve tracts, but the mechanisms involved are generally poorly understood. The calcium-binding protein S100A4 is expressed at elevated levels in cancers, where it has been linked to increased invasion and metastasis. Here we report genetic studies a Drosophila model define effector functions that mediate metastatic dissemination of mutant Ras-induced tumors developing nervous system. In flies overexpressing RasVal12 S100A4, there was...
S100P has been shown to be a marker for carcinogenesis where its expression in solid tumours correlates with metastasis and poor patient prognosis. This protein's role any physiological process is, however, unknown. Here we first show that is expressed both trophoblasts vivo as well some corresponding cell lines culture. We demonstrate predominantly during the early stage of placental formation highest levels occurring trimester gestation, particularly invading columns anchoring villi. Using...
Six novel Open Reading Frames (ORFs) located on the left arm of chromosome XII (YLL061w, YLL060c, YLL059c, YLL058w, YLL057c and YLL056c) have been analysed using either short-flanking homology (SFH) or long-flanking (LFH) gene replacement. Sporulation tetrad analysis showed none these ORFs to be essential for vegetative growth. The standard EUROFAN growth tests failed reveal any obvious phenotypes resulting from deletion each ORFs. Bioinformatic revealed that YLL061w is probably an amino...
S100P protein in human breast cancer cells is associated with reduced patient survival and, a model system of metastasis, it confers metastatic phenotype upon benign mammary tumour cells. possesses C-terminal lysine residue. Using multiwell vitro assay, now shown for the first time to exhibit strong, lysine-dependent activation tissue plasminogen activator (tPA), but not urokinase-catalysed activation. The presence 10 μM calcium ions stimulates tPA 2-fold an S100P-dependent manner....
Deletion, together with basic functional and bioinformatic analyses has been carried out on eight novel ORFs discovered during the sequencing of Saccharomyces cerevisiae genome. Six (YLL049w, YLL051c, YLL052c, YLL053c, YLL054c YLL055w) located left arm, one (YLR130c) right chromosome XII, an eighth ORF (YNL331c) arm XIV, have investigated. were deleted by SFH–PCR gene-replacement strategy. Basic analysis revealed no obvious phenotype for any ORFs. Bioinformatic analysis, however, possible...
Six novel Open Reading Frames (ORFs) located on the left arm of chromosome XII (YLL044w, YLL042c, YLL040c, YLL038c, YLL035w and YLL034c) have been analysed using short-flanking homology (SFH) gene replacement. Sporulation tetrad analysis showed that YLL034c are essential for cell growth; yll035w spores arrested after two or three divisions, while majority yll034c stopped growth within cycles germination. Complementation deletion with its cognate clone, a promoter-substitution experiment,...
Deletion via PCR-mediated gene replacement, together with basic functional and bioinformatic analyses, have been performed on six novel open reading-frames (ORFs) the left arm of chromosome XII Saccharomyces cerevisiae(YLL033w, YLL032c, YLL031c, YLL030c, YLL029w YLL028w). ORF deletion was realized using either a short-flanking homology (SFH) or long-flanking (LFH) replacement cassette in diploid strain FY1679. Sporulation tetrad analysis showed that YLL031c is only essential six. Microscopic...
S100P protein is a potent inducer of metastasis in model system, and its presence cancer cells patients strongly associated with their reduced survival times. A well-established Furth Wistar rat methods for measuring cell migration, specific inhibitors were used to study pathways motility-driven metastasis. Cells expressing C-terminal mutant proteins display markedly-reduced S100P-driven vivo migration vitro. These fail the low focal adhesion numbers observed wild-type S100P, exhibit...
The major problem with cancer is the ability of cells to infiltrate surrounding tissue (invasion) or spread distant organs (metastasis), thereby decreasing patient’s survival. One first steps in process metastasis local spreading invasion from primary tumour and certain Ca2+ -binding proteins S100 family eg, S100A4 S100P, can induce a metastatic phenotype enhance cell migration invasion. Both S100P are expressed at elevated levels several forms including breast, pancreatic, prostate, colon,...
<div>Abstract<p>Many human glandular cancers metastasize along nerve tracts, but the mechanisms involved are generally poorly understood. The calcium-binding protein S100A4 is expressed at elevated levels in cancers, where it has been linked to increased invasion and metastasis. Here we report genetic studies a <i>Drosophila</i> model define effector functions that mediate metastatic dissemination of mutant Ras-induced tumors developing nervous system. In flies...
<p>supplemental materials and methods.</p>
<p>Fig S1 Whole Mounts, Fig S2 Westerns, S3 Male/Female Bsk, S4 Inhibitors, S5 Breast Tumors, S6 MMP2 + Other, S7 MMP2/S100A4, Supp Methods, Figure 5 Legend.</p>
<p>supplemental materials and methods.</p>
<div>Abstract<p>Many human glandular cancers metastasize along nerve tracts, but the mechanisms involved are generally poorly understood. The calcium-binding protein S100A4 is expressed at elevated levels in cancers, where it has been linked to increased invasion and metastasis. Here we report genetic studies a <i>Drosophila</i> model define effector functions that mediate metastatic dissemination of mutant Ras-induced tumors developing nervous system. In flies...
<p>Fig S1 Whole Mounts, Fig S2 Westerns, S3 Male/Female Bsk, S4 Inhibitors, S5 Breast Tumors, S6 MMP2 + Other, S7 MMP2/S100A4, Supp Methods, Figure 5 Legend.</p>
Six novel Open Reading Frames (ORFs) located on the left arm of chromosome XII (YLL044w, YLL042c, YLL040c, YLL038c, YLL035w and YLL034c) have been analysed using short-flanking homology (SFH) gene replacement. Sporulation tetrad analysis showed that YLL034c are essential for cell growth; yll035w spores arrested after two or three divisions, while majority yll034c stopped growth within cycles germination. Complementation deletion with its cognate clone, a promoter-substitution experiment,...
Deletion via PCR-mediated gene replacement, together with basic functional and bioinformatic analyses, have been performed on six novel open reading-frames (ORFs) the left arm of chromosome XII Saccharomyces cerevisiae(YLL033w, YLL032c, YLL031c, YLL030c, YLL029w YLL028w). ORF deletion was realized using either a short-flanking homology (SFH) or long-flanking (LFH) replacement cassette in diploid strain FY1679. Sporulation tetrad analysis showed that YLL031c is only essential six. Microscopic...