A5000491993- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Glioma Diagnosis and Treatment
- Hippo pathway signaling and YAP/TAZ
- Protein Kinase Regulation and GTPase Signaling
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Cellular Mechanics and Interactions
- CAR-T cell therapy research
- Cell Adhesion Molecules Research
- Skin and Cellular Biology Research
- Kruppel-like factors research
- Cancer Research and Treatments
- Fibroblast Growth Factor Research
- Ovarian cancer diagnosis and treatment
- MicroRNA in disease regulation
- Peroxisome Proliferator-Activated Receptors
- Cancer Mechanisms and Therapy
- HER2/EGFR in Cancer Research
- Axon Guidance and Neuronal Signaling
- Virus-based gene therapy research
- Pancreatic and Hepatic Oncology Research
- NF-κB Signaling Pathways
Mayo Clinic in Florida
2015-2025
WinnMed
2013-2025
Jacksonville College
2018-2025
Mayo Clinic
2005-2025
Nemours Children’s Clinic
2013-2023
Mayo Clinic in Arizona
2021
Nemours Children's Clinic
2018
UNC Lineberger Comprehensive Cancer Center
2004-2014
Sylvester Comprehensive Cancer Center
2006-2013
Jacksonville University
2013
Îndirect evidence suggests that p120-catenin (p120) can both positively and negatively affect cadherin adhesiveness. Here we show the p120 gene is mutated in SW48 cells, adhesion system impaired as a direct consequence of insufficiency. Restoring normal levels caused striking reversion from poorly differentiated to cobblestone-like epithelial morphology, indicating crucial role for reactivation E-cadherin function. The rescue efficiency was enhanced by increased p120, reduced presence...
p120ctn is a catenin whose direct binding to the juxtamembrane domain of classical cadherins suggests role in regulating cell–cell adhesion. The has been implicated variety roles including cadherin clustering, cell motility, and neuronal outgrowth, raising possibility that p120 mediates these activities. We have generated minimal mutations this region uncouple E-cadherin–p120 interaction, but do not affect interactions with other catenins. By stable transfection into E-cadherin–deficient...
p120 catenin (p120) is the prototypic member of a growing subfamily Armadillo-domain proteins found at cell-cell junctions and in nuclei. In contrast to functions classical catenins (alpha-catenin, beta-catenin, gamma-catenin/plakoglobin), which have been studied extensively, first clues p120's biological function only recently emerged, its role remains controversial. Nonetheless, it now clear that affects adhesion through interaction with highly conserved juxtamembrane domain cadherins,...
Background Cadherins are essential components of the adherens junction complexes that mediate cell-cell adhesion and regulate cell motility. During tissue morphogenesis, changes in cadherin expression (known as switching) a common mechanism for altering fate. Cadherin switching is also during epithelial tumor progression, where it thought to promote invasion metastasis. E-cadherin predominant expressed tissues, but its very limited normal brain. Methodology/Principal Findings We identified...
Background Clear cell renal carcinoma (ccRCC) is the most common kidney cancer. The purpose of this study to define a biological pathway signature and cellular differentiation program in ccRCC. Methodology We performed gene expression profiling early-stage ccRCC patient-matched normal tissue using Affymetrix HG-U133a HG-U133b GeneChips combined with comprehensive bioinformatic analyses, including analysis. results were validated by real time PCR IHC on two independent sample sets. Cellular...
p120 catenin is a cadherin-associated protein that regulates Rho GTPases and promotes the invasiveness of E-cadherin-deficient cancer cells. Multiple isoforms are expressed in cells via alternative splicing, all them essential for HGF signaling to Rac1. However, only full-length (isoform 1) invasiveness. This selective ability isoform 1 mediated by reduced RhoA activity, both under basal conditions following treatment. All can bind vitro, central binding site. cooperative domain...
p120-catenin (p120<sup>ctn</sup>) interacts with the cytoplasmic tail of cadherins and is thought to regulate cadherin clustering during formation adherens junctions. Several observations suggest that p120 can both positively negatively adhesiveness depending on signals so far remain unidentified. Although tyrosine phosphorylation a leading candidate, role this modification in normal Src-transformed cells remains unknown. Here, as first step toward pinpointing role, we have employed...
Protein kinase C ι (PKCι) has been implicated in Ras signaling, however, a role for PKCι oncogenic Ras-mediated transformation not established. Here, we show that is critical downstream effector of the colonic epithelium. Transgenic mice expressing constitutively active colon are highly susceptible to carcinogen-induced carcinogenesis, whereas kinase-deficient (kdPKCι) resistant both carcinogen- and carcinogenesis. Expression kdPKCι Ras-transformed rat intestinal epithelial cells blocks...
The function of Type 1, classic cadherins depends on their association with the actin cytoskeleton, a connection mediated by alpha- and beta-catenin. phosphorylation state beta-catenin is crucial for its cadherin thus cytoskeleton. We now show that regulated combined activities tyrosine kinase Fer phosphatase PTP1B. phosphorylates PTP1B at 152, regulating binding to continuous dephosphorylation 654. interacts indirectly, through p120ctn. have mapped interaction domains p120ctn peptides...
p120-catenin exists in a membrane-associated cadherin-bound pool, cytosolic pool that affects Rho GTPases, and nuclear is thought to associate with the methylation-relevant transcriptional repressor Kaiso. We show here cytoplasmic p120 can also both directly indirectly microtubule network, traffics along microtubules toward their plus ends. The direct binding required most of armadillo repeats was mutually exclusive for interaction E-cadherin. Perturbing p120-microtubule nocodazole or taxol...
During epithelial tumor progression, the loss of E-cadherin expression and inappropriate mesenchymal cadherins coincide with increased invasiveness. Reexpression experiments have established as an invasion suppressor. However, mechanism by which suppresses invasiveness role are poorly understood. We show that both p120 catenin required for E-cadherin–deficient cells. binding promotes up-regulation activation Rac1, essential cell migration also inhibiting RhoA activity, independently cadherin...
Vascular endothelial growth factor (VEGF) and Ang1 (Angiopoietin-1) have opposing effects on vascular permeability, but the molecular basis of these is not fully known. We report in this paper that VEGF regulate cell (EC) junctions by determining localization RhoA-specific guanine nucleotide exchange Syx. Syx was recruited to members Crumbs polarity complex promoted junction integrity activating Diaphanous. caused translocation from junctions, promoting disassembly, whereas maintained at...
DNA methylation-induced silencing of genes encoding tumor suppressors is common in many types cancer, but little known about how such epigenetic can contribute to metastasis. The PRKD1 gene encodes protein kinase D1 (PKD1), a serine/threonine that expressed cells the normal mammary gland, where it maintains epithelial phenotype by preventing epithelial-to-mesenchymal transition.The status promoter methylation was analyzed reduced representation bisulfite deep sequencing, methylation-specific...
Anti-VEGF antibody therapy with bevacizumab provides significant clinical benefit in patients recurrent glioblastoma multiforme (GBM). Unfortunately, progression on is often associated a diffuse disease recurrence pattern, which limits subsequent therapeutic options. Therefore, there an urgent need to understand bevacizumab's influence glioma biology and block it's actions towards cell invasion. To explore the mechanism(s) of GBM invasion we have examined panel serially transplanted human...
In the liver, cystic fibrosis (CF) transmembrane conductance regulator (CFTR) regulates bile secretion and other functions at apical membrane of biliary epithelial cells (i.e., cholangiocytes). CF‐related liver disease is a major cause death in patients with CF. CFTR dysfunction affects innate immune pathways, generating para‐inflammatory status epithelia. This study investigates mechanisms linking to toll‐like receptor 4 activity. We found that associated multiprotein complex normal mouse...
Src signaling is markedly upregulated in patients with invasive glioblastoma (GBM) after the administration of bevacizumab. The family kinase inhibitor dasatinib has been found to effectively block bevacizumab-induced glioma invasion preclinical models, which led hypothesis that combining bevacizumab could increase efficacy recurrent GBM.After completion phase 1 component, 2 trial (ClinicalTrials.gov identifier NCT00892177) randomized GBM 2:1 receive 100 mg oral twice daily (arm A) or...