A5003483571- RNA modifications and cancer
- Autophagy in Disease and Therapy
- Cancer therapeutics and mechanisms
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Lung Cancer Research Studies
- Genetic and Kidney Cyst Diseases
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Peptidase Inhibition and Analysis
- Cancer-related gene regulation
- Hedgehog Signaling Pathway Studies
- Cytokine Signaling Pathways and Interactions
- Heat shock proteins research
- Microtubule and mitosis dynamics
- Computational Drug Discovery Methods
- Cancer Genomics and Diagnostics
- Circular RNAs in diseases
- Cell Adhesion Molecules Research
- MicroRNA in disease regulation
- Toxin Mechanisms and Immunotoxins
- Cancer, Hypoxia, and Metabolism
- Glycosylation and Glycoproteins Research
- Molecular Biology Techniques and Applications
- Research on Leishmaniasis Studies
University of Alabama at Birmingham
2024
California University of Pennsylvania
2024
Nova Southeastern University
2024
Fox Chase Cancer Center
2015-2024
Kazan Federal University
2015-2022
Significance The evolutionarily conserved RNA-binding protein Musashi-2 (MSI2) regulates mRNA translation and influences multiple biological processes, including maintenance of stem cell identity. This work for the first time, to our knowledge, identifies that more aggressive patient tumors have higher MSI2 levels. We define a critical role in supporting non-small lung cancer (NSCLC) invasiveness further claudins 3, 5, 7 (CLDN3, CLDN5, CLDN7), TGF-β receptor 1 (TGFβR1), small mothers against...
Head and neck squamous cell carcinoma (HNSCC) is a frequently devastating cancer that affects more than half million people annually worldwide. Although some cases arise from infection with human papillomavirus (HPV), HPV-negative HNSCC common, associated worse outcome. Advanced may be treated surgery, chemoradiation, targeted therapy, or immune checkpoint inhibition (ICI). There considerable need for predictive biomarkers these treatments. Defects in DNA repair capacity loss of cell-cycle...
Abstract Non-small cell lung cancer (NSCLC) has limited treatment options. Expression of the RNA-binding protein (RBP) Musashi-2 (MSI2) is elevated in a subset non-small tumors upon progression, and drives NSCLC metastasis. We evaluated mechanism MSI2 action to gain therapeutically useful insights. Reverse phase array (RPPA) analysis MSI2-depleted versus control Kras LA1/+ ; Trp53 R172HΔG/+ lines identified EGFR as MSI2-regulated protein. expression activity an line panel was studied using...
Autosomal-dominant polycystic kidney disease (ADPKD) is associated with progressive formation of renal cysts, enlargement, hypertension, and typically end-stage disease. In ADPKD, inherited mutations disrupt function the polycystins (encoded by PKD1 PKD2), thus causing loss a cyst-repressive signal emanating from cilium. Genetic studies have suggested ciliary maintenance essential for ADPKD pathogenesis. Heat shock protein 90 (HSP90) clients include multiple proteins linked to maintenance....
Abstract In pancreatic ductal adenocarcinoma (PDAC), the fibroblastic stroma constitutes most of tumor mass and is remarkably devoid functional blood vessels. This raises an unresolved question how PDAC cells obtain essential metabolites water-insoluble lipids. We have found a critical role for cancer-associated fibroblasts (CAFs) in obtaining transferring lipids from blood-borne particles to via trogocytosis CAF plasma membranes. also determined that CAF-expressed phospholipid scramblase...
Abstract Purpose: Small cell lung cancer (SCLC) is a highly aggressive disease representing 12% to 13% of total cancers, with median survival <2 years. No targeted therapies have proven effective in SCLC. Although most patients respond initially cytotoxic chemotherapies, resistance rapidly emerges, response second-line agents limited, and dose-limiting toxicities (DLT) are major issue. This study performs preclinical evaluation new compound, STA-8666, Experimental Design: To avoid DLT...
Head and neck squamous cell carcinomas (HNSCC) affect more than 800,000 people annually worldwide, causing over 15,000 deaths in the US. Among HNSCC cancers, human papillomavirus (HPV)-negative has worst outcome, motivating efforts to improve therapy for this disease. The most common mutational events HPV-negative are inactivation of tumor suppressors TP53 (>85%) CDKN2A (>57%), which significantly impairs G1/S checkpoints, reliance on other cycle checkpoints repair ongoing replication...
For many tumors, signaling exchanges between cancer cells and other in their microenvironment influence overall tumor signaling. Some of these depend on expression the primary cilium nontransformed cell populations, as extracellular ligands including Sonic Hedgehog (SHH), PDGFRα, others function through receptors spatially localized to cilia. Cell ciliation is regulated by proteins that are themselves therapeutic targets. We investigated whether kinase inhibitors clinical interest with...
Aurora-A kinase (AURKA) overexpression in numerous tumors induces aneuploidy, part because of cytokinetic defects. Alisertib and other small-molecule inhibitors targeting AURKA are effective some patients as monotherapies or combination therapies. EGFR pro-proliferative signaling activity is commonly elevated cancer, the inhibitor erlotinib used a standard care agent for cancer. An erlotinib/alisertib therapy currently under assessment clinical trials, following pre-clinical studies that...
Abstract Non–small cell lung cancer (NSCLC) is the most common worldwide. With overall 5-year survival estimated at <17%, it critical to identify factors that regulate NSCLC disease prognosis. commonly driven by mutations in KRAS and TP53, with activation of additional kinases such as SRC promoting tumor invasion. In this study, we investigated role NEDD9, a activator scaffolding protein, tumorigenesis. an inducible model dependent on Kras mutation Trp53 loss (KP mice), deletion Nedd9...
Elevated rates of glycolysis in cancer cells support tumor growth, a process that typically depends on oncogene-induced increases the expression and/or activity enzymes glycolytic pathway. The NEDD9 scaffolding protein is upregulated many advanced tumors, with increased promoting SRC and other effectors promote invasion metastasis. We here define new role for glycolysis. knockdown significantly impaired multiple lung cell lines This was accompanied by post-transcriptional downregulation...
Musashi-2 (MSI2) is a member of RNA-binding protein family that regulates mRNA translation numerous intracellular targets and influences maintenance stem cell identity. This study assessed MSI2 as potential clinical biomarker in non-small lung cancer (NSCLC).The current included 40 patients with NSCLC, whom one presented stage 1, 14 II, 15 III, 10 had IV. All received standard care treatments. patient samples were obtained before treatment started. We used immunohistochemical (IHC) approach...
// Anna V. Gaponova 1, 2 , Alexander Y. Deneka Tim N. Beck 3 Hanqing Liu 4 Gregory Andrianov S. Nikonova 1 Emmanuelle Nicolas Margret B. Einarson Erica A. Golemis Ilya G. Serebriiskii Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA Department of Biochemistry and Biotechnology, Kazan Federal University, 420008, Russian Federation & Biology, Program in Cell Biology Genetics, Drexel University College Medicine, 19129, Pharmaceutics, Jiangsu School Pharmacy, Jingkou...
Non-small cell lung cancer (NSCLC) is the leading cause of death worldwide, with a 5-year survival only ~16%. Potential strategies to address NSCLC mortality include improvements in early detection and prevention, development new therapies suitable for use patients late stage diagnoses. Controlling growth tumors could yield significant clinical benefits comorbidities that make them poor candidates surgery: however, many drugs limit are not useful setting long-term or comorbid patients,...
Colorectal cancer (CRC) is one of the most common cancers, with an annual incidence ~135,000 in US, associated ~50,000 deaths. Autosomal dominant polycystic kidney disease (ADPKD), mutations disabling PKD1 gene, affects as many 1 1000. Intriguingly, some studies have suggested that individuals germline reduced CRC, suggesting a genetic modifier function. Using mouse models, we here establish loss Pkd1 greatly reduces CRC and tumor growth induced by suppressor Apc. Growth Pkd1-/-;Apc-/-...
Abstract Lung cancer is one of the most common types worldwide. Non-small cell lung (NSCLC), typically caused by KRAS and TP53 driver mutations, represents majority all new diagnoses. Overexpression RNA-binding protein (RBP) Musashi-2 (MSI2) has been associated with NSCLC progression. To investigate role MSI2 in development, we compared tumorigenesis mice lung-specific Kras -activating mutation Trp53 deletion, without Msi2 deletion (KPM2 versus KP mice). KPM2 showed decreased comparison...
Targeted, catalytic degradation of oncoproteins using heterobifunctional small molecules is an attractive modality, particularly for hematologic malignancies, which are often initiated by aberrant transcription factors and challenging to drug with inhibitors. BRD4, a member the bromodomain extraterminal family, core transcriptional epigenetic regulator that recruits P-TEFb complex, includes Cdk9 cyclin T, RNA polymerase II (pol II). Together, BRD4 CDK9 phosphorylate serine 2 (pSer2) heptad...
6552 Background: The tumor suppressors TP53 and CDKN2A are commonly mutated or lost in HNSCC, impairing G1 checkpoints. This reduces ability to repair DNA damage arising from hypoxia, replication stress, mutagen exposure, thus increasing TMB, a potential predictive biomarker for immunotherapy benefit. mutations can be classified as loss-of-function (LOF) with without dominant negative (DNE) activity, gain-of-function (GOF) benign. We investigated whether specific categories of mutation were...
The RNA-binding protein Musashi-2 (MSI2) controls the translation of proteins that support stem cell identity and lineage determination is associated with progression in some cancers. We assessed MSI2 as potential clinical biomarker colorectal cancer (CRC) tubulovillous adenoma (TA) colon mucosa.
DNA damaging modalities are the backbone of treatments for non-small cell lung cancer (NSCLC). Alterations in damage response (DDR) tumor cells commonly contribute to emerging resistance platinating agents, other targeted therapies, and radiation. The goal this study is identify previously unreported role NEDD9 scaffolding protein controlling DDR processes sensitivity therapies. Using a siRNA-mediated approach deplete group human murine KRAS/TP53-mutant NSCLC lines, coupled with set...
Lung cancer is one of the most common types cancers worldwide. Non-small cell lung (NSCLC), typically caused by KRAS and TP53 driver mutations, represents majority all new diagnoses. Overexpression RNA-binding protein (RBP) Musashi-2 (MSI2) has been associated with NSCLC progression. To investigate role MSI2 in development, we compared tumorigenesis mice lung-specific Kras -activating mutation Trp53 deletion, without Msi2 deletion (KP versus KPM2 mice). showed decreased comparison KP what...