A5053231013- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Caveolin-1 and cellular processes
- Genomics and Rare Diseases
- Peptidase Inhibition and Analysis
- Immune cells in cancer
- Cancer, Lipids, and Metabolism
- Cell Adhesion Molecules Research
- Ferroptosis and cancer prognosis
- Protein Kinase Regulation and GTPase Signaling
- Pancreatic and Hepatic Oncology Research
- Glycosylation and Glycoproteins Research
- TGF-β signaling in diseases
- Cancer-related molecular mechanisms research
- Mechanisms of cancer metastasis
- Monoclonal and Polyclonal Antibodies Research
- Proteoglycans and glycosaminoglycans research
- Nuclear Structure and Function
- Cancer-related gene regulation
- Advanced Proteomics Techniques and Applications
National Cancer Institute
2016-2025
National Institutes of Health
2016-2025
Center for Cancer Research
2012-2025
Leidos (United States)
2022
Leidos Biomedical Research Inc. (United States)
2022
University of Eastern Finland
2022
Cancer Institute (WIA)
2019-2022
National Institute of Neurological Disorders and Stroke
2014
Veterans Health Administration
2003
Scripps Research Institute
1996-2001
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is often used as a stable housekeeping marker for constant gene expression. However, the transcriptional levels of GAPDH may be highly up-regulated in some cancers, including non-small cell lung cancers (NSCLC). Using publically available microarray database, we identified group genes whose expression are correlated with up-regulation. The majority cycle-dependent (GAPDH Associated Cell Cycle, or GACC). up-regulation pattern positively...
DLC1 is a tumor suppressor protein whose full activity depends on its presence at focal adhesions, Rho-GTPase activating (Rho-GAP) function, and ability to bind several ligands, including tensin talin. However, the mechanisms that regulate coordinate these activities remain poorly understood. Here we identify CDK5, predominantly cytoplasmic serine/threonine kinase, as an important regulator of functions. The CDK5 kinase phosphorylates four serines in located N-terminal Rho-GAP domain. When...
The receptor for hyaluronic acid-mediated motility (RHAMM) is upregulated in various cancers, but its role primary and metastatic non-small cell lung carcinoma (NSCLC) remains to be determined. Here, we investigate the clinical relevance of RHAMM expression NSCLC. protein correlates with histological differentiation stages extent tumor (T stages) 156 patients Importantly, while focal staining pattern present 57% NSCLC, intense 96% NSCLC cases. In a publicly available database, Cancer Genome...
The RHO family of RAS-related GTPases in tumors may be activated by reduced levels GTPase accelerating proteins (GAPs). One common mechanism is decreased expression one or more members the Deleted Liver Cancer (DLC) Rho-GAPs, which comprises three closely related genes (DLC1, DLC2, and DLC3) that are down-regulated a wide range malignancies. Here we have studied their comparative biological activity cultured cells used publicly available datasets to examine mRNA patterns normal cancer...
Myeloid cells that orchestrate malignant progression in the tumor microenvironment offer targets for a generalized strategy to attack solid tumors. Through an analysis of microenvironments, we explored experimental model lung cancer uncovered network Dll4/Notch/TGF-β1 signals links myeloid progression. attracted by tumor-derived cytokines CCL2 and M-CSF expressed increased levels Notch ligand Dll4, thereby activating signaling amplifying tumor-intrinsic activation. Heightened Dll4/Notch...
We developed cProSite, a website that provides online genomics, proteomics, and phosphoproteomics analysis for the data of The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC). This tool focuses on comparisons correlations between different proteins mRNAs tumors normal tissues. Our is designed with biologists clinicians in mind, user-friendly environment fast search engine. results cProSite can be used clinical validation provide useful strategic information...
We report several receptor tyrosine kinase (RTK) ligands increase RhoA-guanosine triphosphate (GTP) in untransformed and transformed cell lines determine this phenomenon depends on the RTKs activating AKT serine/threonine kinase. The increased RhoA-GTP results from phosphorylating three serines (S298, S329, S567) DLC1 tumor suppressor, a Rho GTPase-activating protein (RhoGAP) associated with focal adhesions. Phosphorylation of serines, located N-terminal to RhoGAP domain, induces strong...
Allosteric inhibitors of the tyrosine phosphatase SHP2 hold therapeutic promise in cancers with overactive RAS/ERK signaling but "adaptive resistance" to may limit benefits. Here, we utilized tumor cells that proliferate similarly or without endogenous explore means overcome this growth-independence from SHP2. We found depletion profoundly alters output vascular regulators, cytokines, chemokines, and other factors growth-resistant cancer cells. Tumors derived inoculation SHP2-depleted,...
Abstract Metastatic pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis. Identifying useful drug combinations for PDAC treatment an important challenge molecularly targeted therapy. Oncogenic mutations in the KRAS gene, which are found over 90% of patients, play critical role PDAC. Although inhibitors may be treatment, it likely that resistance will develop most patients given single agent treatment. To overcome this anticipated limitation, effective...
Abstract The tumor suppressor gene deleted in liver cancer-1 (DLC1), which encodes a protein with strong RhoGAP (GTPase activating protein) activity and weak Cdc42GAP activity, is inactivated various human malignancies. Following Dlc1 inactivation, mouse embryo fibroblasts (MEF) conditional knockout allele reproducibly underwent neoplastic transformation. In addition to inactivation of increased Rho Cdc42, transformation depended on the subsequent decreased expression Cdk4/6 inhibitors...
Mothers of children with neonatal lupus erythematosus (NLE) and heart block, as well patients Sjögren's syndrome (SS) systemic erythematosus, have serum autoantibodies that recognize SS-A/Ro autoantigens including the 60-kDa ribonucleoprotein. By yeast 2-hybrid screening, we identified a novel 75-kDa protein (pp75) interacts carboxyl 70% SS-A/Ro. The specificity interaction was confirmed using mammalian chemical crosslinking studies. Immunoprecipitation radiolabeled HeLa cell extracts showed...
Endometrial cancer is one of the most common gynecologic malignancies worldwide. Only 2 agents have been approved by Food and Drug Administration for endometrial since 1971. There a need to identify molecular targets treat advanced cancer. The receptor hyaluronic acid–mediated motility (RHAMM) upregulated in various types Here, we aimed determine clinical significance RHAMM expression Two hundred twenty-five cases cancer, including serous endometrioid types, 8 normal endometrium were used...
In advanced cancer, the RHOA GTPase is often active together with reduced expression of genes encoding Rho-specific GTPase-accelerating proteins (Rho-GAP), which negatively regulate and related GTPases. Here we used The Cancer Genome Atlas dataset to examine 12 tumor types (including colon, breast, prostate, pancreas, lung adenocarcinoma, squamous cell carcinoma) for frequency codon mutations 10 Rho-GAP experimentally tested biochemical biological consequences cancer-associated mutants that...
The tyrosine phosphatase SHP2 is oncogenic in cancers driven by receptor-tyrosine-kinases, and inhibition reduces tumor growth. Here, we report that an essential promoter of endothelial cell survival growth the remodeling vasculature. Using genetic chemical approaches to inhibit activity cells, show inhibits pro-apoptotic STAT3 stimulates proliferative ERK1/2 signaling. Systemic mice bearing types selected for SHP2-independent promotes degeneration vasculature blood extravasation;...
DLC1, a tumor suppressor gene that is downregulated in many cancer types by genetic and nongenetic mechanisms, encodes protein whose RhoGAP scaffolding activities contribute to its functions. The role of the DLC1 START (StAR-related lipid transfer; DLC1-START) domain, other than binding Caveolin-1, poorly understood. In domains, key function they bind lipids, but putative ligand for DLC1-START unknown.Lipid overlay assays Phosphatidylserine (PS)-pull down confirmed PS. Co-immunoprecipitation...
Advanced colorectal carcinoma is currently incurable, and new therapies are urgently needed. We report that phosphotyrosine-dependent Eph receptor signaling sustains cell survival, thereby uncovering a survival pathway active in cells. find genetic biochemical inhibition of tyrosine kinase activity or depletion the ligand EphrinB2 reproducibly induces death by autophagy. Spautin 3-methyladenine, inhibitors early steps autophagic pathway, significantly reduce autophagy-mediated follows cancer...
SRC and ERK kinases control many cell biological processes that promote tumorigenesis by altering the activity of oncogenic tumor suppressor proteins. We identify here a physiological interaction between DLC1, focal adhesion protein suppressor, with ERK. The function DLC1 is attenuated phosphorylation tyrosines Y451 Y701 SRC, which down-regulates DLC1's tensin-binding Rho-GAP activities. ERK1/2 phosphorylate on serine S129, increases both binding to SRC-dependent DLC1. inhibitors exhibit...