A5090179644- Colorectal Cancer Treatments and Studies
- HER2/EGFR in Cancer Research
- Liver physiology and pathology
- Hepatocellular Carcinoma Treatment and Prognosis
- Lung Cancer Treatments and Mutations
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Neuroblastoma Research and Treatments
- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- Metabolomics and Mass Spectrometry Studies
- Spectroscopy Techniques in Biomedical and Chemical Research
- Gastric Cancer Management and Outcomes
- Molecular Biology Techniques and Applications
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Gene expression and cancer classification
- Cancer Genomics and Diagnostics
- Pancreatic function and diabetes
- Computational Drug Discovery Methods
- TGF-β signaling in diseases
- Circular RNAs in diseases
- Ubiquitin and proteasome pathways
Vanderbilt University
2011-2024
Vanderbilt University Medical Center
2013-2024
Nashville Oncology Associates
2020
Max Planck Institute of Biochemistry
2008
Institute of Genomics and Integrative Biology
2003
<ns4:p>Seven ligands bind to and activate the mammalian epidermal growth factor (EGF) receptor (EGFR/ERBB1/HER1): EGF, transforming factor-alpha (TGFA), heparin-binding EGF-like (HBEGF), betacellulin (BTC), amphiregulin (AREG), epiregulin (EREG), epigen (EPGN). Of these, TGFA, HBEGF, BTC are thought be high-affinity ligands, whereas AREG, EREG, EPGN constitute low-affinity ligands. This focused review is meant highlight recent studies related actions of individual EGFR interesting biology...
De novo and acquired resistance are major impediments to the efficacy of conventional targeted cancer therapy. In unselected gastric (GC) patients with advanced disease, trials combining chemotherapy an anti-EGFR monoclonal antibody have been largely unsuccessful. effort identify biomarkers so as better select for such trials, we screened secretome chemotherapy-treated human GC cell lines. We found that levels CGA, α-subunit glycoprotein hormones, were markedly increased in conditioned media...
Abstract Although amplifications and mutations in receptor tyrosine kinases (RTKs) act as bona fide oncogenes, most cancers, RTKs maintain moderate expression remain wild-type. Consequently, cognate ligands control many facets of tumorigenesis, including resistance to anti-RTK therapies. Herein, we show that the for MET RON, HGF HGFL, respectively, are synthesized inactive precursors activated by cellular proteases. Our newly generated HGF/HGFL protease inhibitors could overcome both de novo...
Abstract Despite numerous screening tools for colorectal cancer (CRC), 25 % of patients are diagnosed with advanced disease. Novel diagnostic technologies that early, accurate, and rapid imperative to assess the therapeutic efficacy clinical drugs identify new biomarkers treatment response. Here Raman spectroscopy (RS) was used track metabolic reprogramming in KRAS‐mutant HCT116 SW837 cells, KRAS wild‐type CC cells. RS combined multivariate analysis methods distinguished nonresponsive,...
Resistance to clinical therapies remains a major barrier in cancer management. There is critical need for rapid and highly sensitive diagnostic tools that enable early prediction of treatment response allow accurate decisions. Here, Raman spectroscopy was employed monitor changes key metabolites as predictors KRAS-mutant colorectal (CRC) cells, HCT116, treated with chemotherapies. We show at the single cell level HCT116 resistant cetuximab (CTX), first-line CRC, but this resistance can be...
Exposure to extensive ultraviolet (UV) rays is a major cause of skin cancer, which thought be initiated by DNA mutations. Members the epidermal growth factor receptor (EGFR) family are important in various pathophysiologic processes like cancer and shown phosphorylated upon UV exposure. Here we show that EGFR phosphorylation modest doses dependent on metalloprotease activity resultant (EGF) proligand shedding. This cleavage releases mature ligand, then binds activates EGFR. We induced...
Significance By culturing a human colorectal cancer (CRC) cell line (HCA-7) in 3D, we have generated two lines (CC and SC) with distinct morphological, genetic, biochemical, functional properties. Using this 3D system, discovered that increased tyrosine phosphorylation of MET RON results cetuximab resistance the SC can be overcome by addition dual MET/RON kinase inhibitor, crizotinib. We also identified epithelial, but not stromal, versican staining correlates reduced survival clinically...
Epithelial cells establish apical and basolateral (BL) membranes with distinct protein lipid compositions. To achieve this spatial asymmetry, the cell utilizes a variety of mechanisms for differential sorting, delivery retention surface proteins. The EGF receptor (EGFR) its ligand, amphiregulin (AREG), are transmembrane proteins delivered to BL membrane in polarized epithelial cells. Herein, we show that cytoplasmic domain AREG (ACD) contains dominant sorting information; replacement...
Establishment and maintenance of apico-basolateral trafficking pathways are critical to epithelial homeostasis. Loss polarity fidelity thought occur as a consequence transformation; however, here we report that selective mistrafficking the epidermal growth factor receptor (EGFR) ligand epiregulin (EREG) from basolateral apical cell surface drives transformation. Normally, EREG is preferentially delivered polarized Madin-Darby canine kidney cells. regulated by conserved tyrosine-based sorting...
Rapid and accurate response to targeted therapies is critical differentiate tumors that are resistant treatment early in the regimen.
Abstract Many multicenter randomized clinical trials in oncology are conducted through the National Clinical Trials Network (NCTN), an organization consisting of 5 cooperative groups. These groups made up multidisciplinary investigators who work collaboratively to conduct that test novel therapies and establish best practice for cancer care. Unfortunately, disparities trial leadership evident. To examine current state diversity, equity, inclusion across NCTN, independent NCTN Task Force...
Apicobasolateral polarity is a fundamental property of epithelial cells, and its loss hallmark cancer. Integrin-mediated contact with the extracellular matrix defines basal surface, setting in motion E-cadherin-mediated cell-cell contact, which establishes apicobasolateral polarity. Role(s) for lateral integrins this polarization process consequences their disruption are incompletely understood. We show that addition an integrin β1-activating monoclonal antibody, P4G11, to invasive...
It is increasingly appreciated that 3D cultures are more predictive of in vivo therapeutic efficacy than 2D cultures. Using vitro type I collagen human colorectal cancer (CRC) cell line HCA-7 derivatives CC, SC, and CC-CR, we previously identified activation receptor tyrosine kinases (RTKs) MET RON contributed to resistance the EGF (EGFR)-directed antibody cetuximab. The de novo mode cetuximab SC cells could be overcome by crizotinib, a multi-RTK inhibitor also targets RON. We now show...
Directed delivery of EGF receptor (EGFR) ligands to the apical or basolateral surface is a crucial regulatory step in initiation EGFR signaling polarized epithelial cells. Herein, we show that ligand, betacellulin (BTC), preferentially sorted MDCK By sequential truncations and site-directed mutagenesis within BTC cytoplasmic domain, combined with selective cell-surface biotinylation immunofluorescence, have uncovered monoleucine-based sorting motif (EEXXXL:E156EMETL). Disruption this led...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTParticle Deposition Due to Thermal Force in the Tranition and Near-Continuum RegimesBhuminder Singh R. Lee ByersCite this: Ind. Eng. Chem. Fundamen. 1972, 11, 1, 127–133Publication Date (Print):February 1972Publication History Published online1 May 2002Published inissue 1 February 1972https://pubs.acs.org/doi/10.1021/i160041a019https://doi.org/10.1021/i160041a019research-articleACS PublicationsRequest reuse permissionsArticle...
The classic mode of G protein-coupled receptor (GPCR)-mediated transactivation the tyrosine kinase epidermal growth factor (EGFR) occurs via matrix metalloprotease (MMP)-mediated cleavage plasma membrane-anchored EGFR ligands. Herein, we show that Gαs-activating GPCR ligands vasoactive intestinal peptide (VIP) and prostaglandin E2 (PGE2 ) transactivate through increased cell-surface delivery ligand transforming factor-α (TGFα) in polarizing madin-darby canine kidney (MDCK) Caco-2 cells. This...
Abstract As a key process within the tissue microenvironment, integrin signaling can influence cell functional responses to growth factor stimuli. We show here that clustering of α5ß1 at plasma membrane colorectal cancer-derived epithelial cells modulates their ability respond stimulation by receptor tyrosine kinase (RTK)-activating factors EGF, NRG and HGF, through GSK3-mediated suppression Akt pathway. observed is lost from poorly organized human tumors treatment with integrin-clustering...
Delivery to the correct membrane domain in polarized epithelial cells is a critical regulatory mechanism for transmembrane proteins. The trafficking of these proteins directed by short amino acid sequences known as sorting motifs. In six basolaterally-localized lacking canonical tyrosine- and dileucine-based basolateral motifs, monoleucine-based motif has been identified. This review will discuss with an identified motif, their conserved structural features, well future directions study this...