A5059325982- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- Pancreatic and Hepatic Oncology Research
- Chromatin Remodeling and Cancer
- Phagocytosis and Immune Regulation
- Cholangiocarcinoma and Gallbladder Cancer Studies
- MXene and MAX Phase Materials
- Hedgehog Signaling Pathway Studies
- Mechanisms of cancer metastasis
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- Chronic Lymphocytic Leukemia Research
- Cardiac Fibrosis and Remodeling
- Cancer-related gene regulation
- Lymphoma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Glycosylation and Glycoproteins Research
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Acute Myeloid Leukemia Research
- Click Chemistry and Applications
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Signaling Pathways in Disease
- Organ Transplantation Techniques and Outcomes
Novel (United States)
2015-2024
Mayo Clinic
2015-2024
Mayo Clinic in Florida
2010-2019
Mayo Clinic in Arizona
2010-2019
WinnMed
2010-2012
Institute of Molecular Biology
2011-2012
University of Pittsburgh
2010
National University of Rosario
2002-2009
Although the biological role of KRAS is clearly established in carcinogenesis, molecular mechanisms underlying this phenomenon are not completely understood. In study, we provide evidence a novel signaling network regulated by transcription factor GLI1 mediating KRAS-induced carcinogenesis. Using pancreatic cancer (a disease with high prevalence <i>KRAS</i> mutations) as model, show that loss blocks progression preneoplastic lesions mice pancreas-specific Cre-activated oncogenic mutant...
Understanding the molecular events controlling melanoma progression is of paramount importance for development alternative treatment options this devastating disease. Here we report a mechanism regulated by oncogenic SOX2-GLI1 transcriptional complex driving invasion through induction sialyltransferase ST3GAL1. Using in vitro and vivo studies, demonstrate that ST3GAL1 drives metastasis. Silencing enzyme suppresses significantly reduces ability aggressive cells to enter blood stream, colonize...
SP/KLF (Specificity protein/Krüppel-like factor) transcription factors comprise an emerging group of proteins that may behave as tumour suppressors. Incidentally, many cancers display alterations in certain KLF are also associated with a high incidence KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue) mutations. Therefore the present paper we investigate whether suppress KRAS-mediated cell growth, and more importantly, potential mechanisms underlying these effects. Using...
Objective Despite advances in the identification of epigenetic alterations pancreatic cancer, their biological roles pathobiology this dismal neoplasm remain elusive. Here, we aimed to characterise functional significance histone lysine methyltransferases (KMTs) and demethylases (KDMs) tumourigenesis. Design DNA methylation sequencing gene expression microarrays were employed investigate CpG patterns KMTs KDMs cancer tissues versus normal tissues. Gene was assessed five cohorts patients by...
The role of the epithelial-to-mesenchymal transition (EMT) during hepatocellular carcinoma (HCC) progression is well established, however regulatory mechanisms modulating this phenomenon remain unclear. Here, we demonstrate that transcription factor glioma-associated oncogene 1 (GLI1) modulates EMT through direct up-regulation SNAI1 and serves as a downstream effector transforming growth factor-β1 (TGFβ1) pathway, well-known regulator in cancer cells. Overexpression GLI1 increased...
Abstract The Hedgehog (HH) pathway has been identified as an important deregulated signal transduction in pancreatic ductal adenocarcinoma (PDAC), a cancer type characterized by highly metastatic phenotype. In PDAC, the canonical HH activity is restricted to stromal compartment while signaling tumor cells reduced consequence of constitutive KRAS activation. Here, we report that PDAC effector transcription factor GLI1 regulates epithelial differentiation. RNAi-mediated knockdown abolished...
Abstract Existing antiangiogenic approaches to treat metastatic hepatocellular carcinoma (HCC) are weakly effectual, prompting further study of tumor angiogenesis in this disease setting. Here, we report a novel role for sulfatase 2 (SULF2) driving HCC angiogenesis. Sulf2-deficient mice (Sulf2 KO) exhibited resistance diethylnitrosamine-induced and did not develop metastases like wild-type WT). The smaller less numerous tumors formed Sulf2 KO markedly lower microvascular density. In human...
<p>Supplementary Figure 8 shows the expression of GLI target genes in all experimental groups.</p>
<p>Supplementary Figure 1 shows correlation of SNP rs1992901 and GLI2 Transcript Expression.</p>
<p>Supplementary Figure 2 describes the characterization of impact Gli2 overexpression in pancreas development. showing that loss has no on development or survival vivo.</p>
<p>Supplementary Figure 3 shows Gli2 expression in CRG and KCRG mice Gli luciferase activity ΔNGli2-transfected cells.</p>
<p>Supplementary Figure 6 describes RNA-seq shows differential gene expression induced by oncogenic KRAS.</p>
<p>Supplementary Figure 7 shows how oncogenic KRAS modulates GLI target gene expression.</p>
<p>Supplementary Figure 9 shows that Gli2 does not change H3K27Ac enrichment at Ccnd1 promoter downstream of oncogenic KRAS.</p>
<p>Supplementary Figure 5 shows the IHC results looking at CD4 and CD8 expression in KC KCRG mice. The show no difference immune landscape between these mouse models.</p>
<p>Supplementary Figure 10 shows not differences in H3K4me1 enrichment at Ccnd1 promoter mutant KRAS cells.</p>
<p>Supplementary Figure 4 shows the validation of Kras signaling activation and chronic pancreatitis phenotypic examples in KC KCRG mice.</p>