Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 21 to 30 of 145

Publication Record

Connections

p120 Catenin is required for normal tubulogenesis but not epithelial integrity in developing mouse pancreas.
Hendley AM, Provost E, Bailey JM, Wang YJ, Cleveland MH, Blake D, Bittman RW, Roeser JC, Maitra A, Reynolds AB, Leach SD
(2015) Dev Biol 399: 41-53
MeSH Terms: Adherens Junctions, Animals, Animals, Newborn, Cadherins, Catenins, Cytoskeleton, Epithelial Cells, Epithelium, Female, Fluorescent Antibody Technique, Gene Expression Regulation, Developmental, Male, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Microscopy, Confocal, Pancreas, Pancreatitis, Chronic, Reverse Transcriptase Polymerase Chain Reaction, alpha Catenin, beta Catenin
Show Abstract · Added February 19, 2015
The intracellular protein p120 catenin aids in maintenance of cell-cell adhesion by regulating E-cadherin stability in epithelial cells. In an effort to understand the biology of p120 catenin in pancreas development, we ablated p120 catenin in mouse pancreatic progenitor cells, which resulted in deletion of p120 catenin in all epithelial lineages of the developing mouse pancreas: islet, acinar, centroacinar, and ductal. Loss of p120 catenin resulted in formation of dilated epithelial tubules, expansion of ductal epithelia, loss of acinar cells, and the induction of pancreatic inflammation. Aberrant branching morphogenesis and tubulogenesis were also observed. Throughout development, the phenotype became more severe, ultimately resulting in an abnormal pancreas comprised primarily of duct-like epithelium expressing early progenitor markers. In pancreatic tissue lacking p120 catenin, overall epithelial architecture remained intact; however, actin cytoskeleton organization was disrupted, an observation associated with increased cytoplasmic PKCζ. Although we observed reduced expression of adherens junction proteins E-cadherin, β-catenin, and α-catenin, p120 catenin family members p0071, ARVCF, and δ-catenin remained present at cell membranes in homozygous p120(f/f) pancreases, potentially providing stability for maintenance of epithelial integrity during development. Adult mice homozygous for deletion of p120 catenin displayed dilated main pancreatic ducts, chronic pancreatitis, acinar to ductal metaplasia (ADM), and mucinous metaplasia that resembles PanIN1a. Taken together, our data demonstrate an essential role for p120 catenin in pancreas development.
Copyright © 2014 Elsevier Inc. All rights reserved.
1 Communities
1 Members
0 Resources
21 MeSH Terms
CD148 tyrosine phosphatase promotes cadherin cell adhesion.
Takahashi K, Matafonov A, Sumarriva K, Ito H, Lauhan C, Zemel D, Tsuboi N, Chen J, Reynolds A, Takahashi T
(2014) PLoS One 9: e112753
MeSH Terms: Cadherins, Cell Adhesion, Cell Line, Drosophila Proteins, Humans, Phosphorylation, Receptor-Like Protein Tyrosine Phosphatases, Class 3, Tyrosine, beta Catenin, cdc42 GTP-Binding Protein, rac GTP-Binding Proteins, rhoA GTP-Binding Protein
Show Abstract · Added February 12, 2015
CD148 is a transmembrane tyrosine phosphatase that is expressed at cell junctions. Recent studies have shown that CD148 associates with the cadherin/catenin complex and p120 catenin (p120) may serve as a substrate. However, the role of CD148 in cadherin cell-cell adhesion remains unknown. Therefore, here we addressed this issue using a series of stable cells and cell-based assays. Wild-type (WT) and catalytically inactive (CS) CD148 were introduced to A431D (lacking classical cadherins), A431D/E-cadherin WT (expressing wild-type E-cadherin), and A431D/E-cadherin 764AAA (expressing p120-uncoupled E-cadherin mutant) cells. The effects of CD148 in cadherin adhesion were assessed by Ca2+ switch and cell aggregation assays. Phosphorylation of E-cadherin/catenin complex and Rho family GTPase activities were also examined. Although CD148 introduction did not alter the expression levels and complex formation of E-cadherin, p120, and β-catenin, CD148 WT, but not CS, promoted cadherin contacts and strengthened cell-cell adhesion in A431D/E-cadherin WT cells. This effect was accompanied by an increase in Rac1, but not RhoA and Cdc42, activity and largely diminished by Rac1 inhibition. Further, we demonstrate that CD148 reduces the tyrosine phosphorylation of p120 and β-catenin; causes the dephosphorylation of Y529 suppressive tyrosine residue in Src, a well-known CD148 site, increasing Src activity and enhancing the phosphorylation of Y228 (a Src kinase site) in p120, in E-cadherin contacts. Consistent with these findings, CD148 dephosphorylated both p120 and β-catenin in vitro. The shRNA-mediated CD148 knockdown in A431 cells showed opposite effects. CD148 showed no effects in A431D and A431D/E-cadherin 764AAA cells. In aggregate, these findings provide the first evidence that CD148 promotes E-cadherin adhesion by regulating Rac1 activity concomitant with modulation of p120, β-catenin, and Src tyrosine phosphorylation. This effect requires E-cadherin and p120 association.
1 Communities
2 Members
0 Resources
12 MeSH Terms
Wnt signaling induces gene expression of factors associated with bone destruction in lung and breast cancer.
Johnson RW, Merkel AR, Page JM, Ruppender NS, Guelcher SA, Sterling JA
(2014) Clin Exp Metastasis 31: 945-59
MeSH Terms: Animals, Blotting, Western, Bone Neoplasms, Breast Neoplasms, Female, Gene Expression Regulation, Humans, Kruppel-Like Transcription Factors, Lung Neoplasms, Mice, Mice, Nude, Nuclear Proteins, Parathyroid Hormone-Related Protein, Promoter Regions, Genetic, RNA, Messenger, RNA, Small Interfering, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Stromal Cells, Transforming Growth Factor beta, Tumor Cells, Cultured, Wnt3A Protein, Xenograft Model Antitumor Assays, Zinc Finger Protein Gli2, beta Catenin
Show Abstract · Added February 12, 2015
Parathyroid hormone-related protein (PTHrP) is an important regulator of bone destruction in bone metastatic tumors. Transforming growth factor-beta (TGF-β) stimulates PTHrP production in part through the transcription factor Gli2, which is regulated independent of the Hedgehog signaling pathway in osteolytic cancer cells. However, inhibition of TGF-β in vivo does not fully inhibit tumor growth in bone or tumor-induced bone destruction, suggesting other pathways are involved. While Wnt signaling regulates Gli2 in development, the role of Wnt signaling in bone metastasis is unknown. Therefore, we investigated whether Wnt signaling regulates Gli2 expression in tumor cells that induce bone destruction. We report here that Wnt activation by β-catenin/T cell factor 4 (TCF4) over-expression or lithium chloride (LiCl) treatment increased Gli2 and PTHrP expression in osteolytic cancer cells. This was mediated through the TCF and Smad binding sites within the Gli2 promoter as determined by promoter mutation studies, suggesting cross-talk between TGF-β and Wnt signaling. Culture of tumor cells on substrates with bone-like rigidity increased Gli2 and PTHrP production, enhanced autocrine Wnt activity and led to an increase in the TCF/Wnt signaling reporter (TOPFlash), enriched β-catenin nuclear accumulation, and elevated Wnt-related genes by PCR-array. Stromal cells serve as an additional paracrine source of Wnt ligands and enhanced Gli2 and PTHrP mRNA levels in MDA-MB-231 and RWGT2 cells in vitro and promoted tumor-induced bone destruction in vivo in a β-catenin/Wnt3a-dependent mechanism. These data indicate that a combination of matrix rigidity and stromal-secreted factors stimulate Gli2 and PTHrP through Wnt signaling in osteolytic breast cancer cells, and there is significant cross-talk between the Wnt and TGF-β signaling pathways. This suggests that the Wnt signaling pathway may be a potential therapeutic target for inhibiting tumor cell response to the bone microenvironment and at the very least should be considered in clinical regimens targeting TGF-β signaling.
1 Communities
3 Members
0 Resources
26 MeSH Terms
Activation of Wnt/β-catenin signaling in a subpopulation of murine prostate luminal epithelial cells induces high grade prostate intraepithelial neoplasia.
Valkenburg KC, Yu X, De Marzo AM, Spiering TJ, Matusik RJ, Williams BO
(2014) Prostate 74: 1506-20
MeSH Terms: Adenomatous Polyposis Coli Protein, Animals, Castration, Enzyme-Linked Immunosorbent Assay, Epithelial Cells, Immunohistochemistry, Male, Mice, Prostate, Prostatic Intraepithelial Neoplasia, Prostatic Neoplasms, Reverse Transcriptase Polymerase Chain Reaction, Tamoxifen, Wnt Proteins, Wnt Signaling Pathway, beta Catenin
Show Abstract · Added January 20, 2015
BACKGROUND - Wnt/β-catenin signaling is important for prostate development and cancer in humans. Activation of this pathway in differentiated luminal cells of mice induces high-grade prostate intraepithelial neoplasia (HGPIN). Though the cell of origin of prostate cancer has yet to be conclusively identified, a castration-resistant Nkx3.1-expressing cell (CARN) may act as a cell of origin for prostate cancer.
METHODS - To activate Wnt/β-catenin signaling in CARNs, we crossed mice carrying tamoxifen-inducible Nkx3.1-driven Cre to mice containing loxP sites in order to either conditionally knock out adenomatous polyposis coli (Apc) or constitutively activate β-catenin directly. We then castrated and hormonally regenerated these mice to target the CARN population.
RESULTS - Loss of Apc in hormonally normal mice induced HGPIN; however, after one or more rounds of castration and hormonal regeneration, Apc-null CARNs disappeared. Alternatively, when β-catenin was constitutively activated under the same conditions, HGPIN was apparent.
CONCLUSION - Activation of Wnt/β-catenin signaling via Apc deletion is sufficient to produce HGPIN in hormonally normal mice. Loss of Apc may destabilize the CARN population under regeneration conditions. When β-catenin is constitutively activated, HGPIN occurs in hormonally regenerated mice. A second genetic hit is likely required to cause progression to carcinoma and metastasis.
© 2014 Wiley Periodicals, Inc.
1 Communities
1 Members
0 Resources
16 MeSH Terms
Helicobacter pylori targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells.
Wroblewski LE, Piazuelo MB, Chaturvedi R, Schumacher M, Aihara E, Feng R, Noto JM, Delgado A, Israel DA, Zavros Y, Montrose MH, Shroyer N, Correa P, Wilson KT, Peek RM
(2015) Gut 64: 720-30
MeSH Terms: Animals, Cell Proliferation, Cells, Cultured, Claudins, Coculture Techniques, Epithelial Cells, Gastric Mucosa, Helicobacter Infections, Helicobacter pylori, Humans, Mice, Inbred C57BL, Snail Family Transcription Factors, Transcription Factors, beta Catenin
Show Abstract · Added January 20, 2015
OBJECTIVE - Helicobacter pylori strains that express the oncoprotein CagA augment risk for gastric cancer. However, the precise mechanisms through which cag(+) strains heighten cancer risk have not been fully delineated and model systems that recapitulate the gastric niche are critical for understanding pathogenesis. Gastroids are three-dimensional organ-like structures that provide unique opportunities to study host-H. pylori interactions in a preclinical model. We used gastroids to inform and direct in vitro studies to define mechanisms through which H. pylori modulates expression of the cancer-associated tight junction protein claudin-7.
DESIGN - Gastroids were infected by luminal microinjection, and MKN28 gastric epithelial cells were cocultured with H. pylori wild-type cag(+) strains or isogenic mutants. β-catenin, claudin-7 and snail localisation was determined by immunocytochemistry. Proliferation was assessed using 5-ethynyl-2'-deoxyuridine, and levels of claudin-7 and snail were determined by western blot and flow cytometry.
RESULTS - Gastroids developed into a self-organising differentiation axis and H. pylori induced mislocalisation of claudin-7 and increased proliferation in a CagA- and β-catenin-dependent manner. In MKN28 cells, H pylori-induced suppression of claudin-7 was regulated by β-catenin and snail. Similarly, snail expression was increased and claudin-7 levels were decreased among H. pylori-infected individuals.
CONCLUSIONS - H. pylori increase proliferation in a strain-specific manner in a novel gastroid system. H. pylori also alter expression and localisation of claudin-7 in gastroids and human epithelial cells, which is mediated by β-catenin and snail activation. These data provide new insights into molecular interactions with carcinogenic potential that occur between H. pylori and epithelial cells within the gastric niche.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
0 Communities
4 Members
0 Resources
14 MeSH Terms
Activation of β-catenin signalling by TFF1 loss promotes cell proliferation and gastric tumorigenesis.
Soutto M, Peng D, Katsha A, Chen Z, Piazuelo MB, Washington MK, Belkhiri A, Correa P, El-Rifai W
(2015) Gut 64: 1028-39
MeSH Terms: Animals, Cell Line, Tumor, Cell Proliferation, Down-Regulation, Glycogen Synthase Kinase 3, Glycogen Synthase Kinase 3 beta, Growth Inhibitors, Immunohistochemistry, Mice, Mice, Knockout, Peptides, Protein Phosphatase 2, Proto-Oncogene Proteins c-akt, Stomach Neoplasms, Transcriptional Activation, Trefoil Factor-1, beta Catenin
Show Abstract · Added February 19, 2015
OBJECTIVE - In this study, we investigated the role of Trefoil factor 1 (TFF1) in regulating cell proliferation and tumour development through β-catenin signalling using in vivo and in vitro models of gastric tumorigenesis.
DESIGN - Tff1-knockout (Tff1-KO) mice, immunohistochemistry, luciferase reporter, qRT-PCR, immunoblot, and phosphatase assays were used to examine the role of TFF1 on β-catenin signalling pathway.
RESULTS - Nuclear localisation of β-catenin with transcriptional upregulation of its target genes, c-Myc and Ccnd1, was detected in hyperplastic tissue at an early age of 4-6 weeks and maintained during all stages of gastric tumorigenesis in the Tff1-KO mice. The reconstitution of TFF1 or TFF1 conditioned media significantly inhibited the β-catenin/T-cell factor (TCF) transcription activity in MKN28 gastric cancer cells. In agreement with these results, we detected a reduction in the levels of nuclear β-catenin with downregulation of c-MYC and CCND1 mRNA. Analysis of signalling molecules upstream of β-catenin revealed a decrease in phosphorylated glycogen synthase kinase 3β (p-GSK3β) (Ser9) and p-AKT (Ser473) protein levels following the reconstitution of TFF1 expression; this was consistent with the increase of p-β-catenin (Ser33/37/Thr41) and decrease of p-β-catenin (Ser552). This TFF1-induced reduction in phosphorylation of GSK3β, and AKT was dependent on protein phosphatase 2A (PP2A) activity. The treatment with okadaic acid or knockdown of PP2A abrogated these effects. Consistent with the mouse data, we observed loss of TFF1 and an increase in nuclear localisation of β-catenin in stages of human gastric tumorigenesis.
CONCLUSIONS - Our data indicate that loss of TFF1 promotes β-catenin activation and gastric tumorigenesis through regulation of PP2A, a major regulator of AKT-GSK3β signalling.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
0 Communities
2 Members
0 Resources
17 MeSH Terms
Effects of phonation time and magnitude dose on vocal fold epithelial genes, barrier integrity, and function.
Kojima T, Valenzuela CV, Novaleski CK, Van Deusen M, Mitchell JR, Garrett CG, Sivasankar MP, Rousseau B
(2014) Laryngoscope 124: 2770-8
MeSH Terms: Animals, Cadherins, Cyclooxygenase 2, Disease Models, Animal, Follow-Up Studies, Gene Expression Regulation, Interleukin-1beta, Microscopy, Electron, Scanning, Occludin, Phonation, RNA, Messenger, Rabbits, Real-Time Polymerase Chain Reaction, Time Factors, Transforming Growth Factor beta1, Vocal Cords, beta Catenin
Show Abstract · Added February 12, 2015
OBJECTIVES/HYPOTHESIS - To investigate the effects of increasing time and magnitude doses of vibration exposure on transcription of the vocal fold's junctional proteins, structural alterations, and functional tissue outcomes.
STUDY DESIGN - Animal study.
METHODS - 100 New Zealand White breeder rabbits were studied. Dependent variables were measured in response to increasing time doses (30, 60, or 120 minutes) and magnitude doses (control, modal intensity, and raised intensity) of vibration exposure. Messenger RNA expression of occludin, zonula occluden-1 (ZO-1), E-cadherin, β-catenin, interleukin 1β, cyclooxygenase-2, transforming growth factor β-1, and fibronectin were measured. Tissue structural alterations were assessed using transmission electron microscopy (TEM). Transepithelial resistance was used to measure functional tissue outcomes.
RESULTS - Occludin gene expression was downregulated in vocal folds exposed to 120-minute time doses of raised-intensity phonation, relative to control, and modal-intensity phonation. ZO-1 gene expression was upregulated following a 120-minute time dose of modal-intensity phonation, compared to control, and downregulated after a 120-minute time dose of raised-intensity phonation, compared to modal-intensity phonation. E-cadherin gene expression was downregulated after a 120-minute time dose of raised-intensity phonation, compared to control and modal-intensity phonation. TEM revealed extensive desquamation of the stratified squamous epithelial cells with increasing time and magnitude doses of vibration exposure. A general observation of lower transepithelial resistance measures was made in tissues exposed to raised-intensity phonation compared to all other groups.
CONCLUSIONS - This study provides evidence of vocal fold tissue responses to varying time and magnitude doses of vibration exposure.
LEVEL OF EVIDENCE - NA.
© 2014 The American Laryngological, Rhinological and Otological Society, Inc.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Reconstitution Of β-catenin degradation in Xenopus egg extract.
Chen TW, Broadus MR, Huppert SS, Lee E
(2014) J Vis Exp :
MeSH Terms: Animals, Female, Ovum, Xenopus laevis, beta Catenin
Show Abstract · Added November 2, 2015
Xenopus laevis egg extract is a well-characterized, robust system for studying the biochemistry of diverse cellular processes. Xenopus egg extract has been used to study protein turnover in many cellular contexts, including the cell cycle and signal transduction pathways(1-3). Herein, a method is described for isolating Xenopus egg extract that has been optimized to promote the degradation of the critical Wnt pathway component, β-catenin. Two different methods are described to assess β-catenin protein degradation in Xenopus egg extract. One method is visually informative ([(35)S]-radiolabeled proteins), while the other is more readily scaled for high-throughput assays (firefly luciferase-tagged fusion proteins). The techniques described can be used to, but are not limited to, assess β-catenin protein turnover and identify molecular components contributing to its turnover. Additionally, the ability to purify large volumes of homogenous Xenopus egg extract combined with the quantitative and facile readout of luciferase-tagged proteins allows this system to be easily adapted for high-throughput screening for modulators of β-catenin degradation.
0 Communities
1 Members
0 Resources
5 MeSH Terms
Progress made in the use of animal models for the study of high-risk, nonmuscle invasive bladder cancer.
Lin-Tsai O, Taylor JA, Clark PE, Adam RM, Wu XR, DeGraff DJ
(2014) Curr Opin Urol 24: 512-6
MeSH Terms: Animals, Carcinoma, Transitional Cell, Disease Models, Animal, Female, Hedgehog Proteins, Male, Mice, Mice, Transgenic, Risk Factors, Sex Factors, Signal Transduction, Tumor Microenvironment, Urinary Bladder Neoplasms, Wnt Proteins, beta Catenin
Show Abstract · Added February 12, 2015
PURPOSE OF REVIEW - High-risk, nonmuscle invasive bladder cancer (HR-NMIBC) represents a costly and difficult-to-treat disease, the molecular pathogenesis of which has a limited understanding. Most preclinical models for the study of bladder cancer are more appropriate for the study of advanced disease. However, recent key advances in preclinical animal models places us at an opportune position to better understand HR-NMIBC.
RECENT FINDINGS - Discoveries in the basic sciences allow us to better understand tumor biology when building models of bladder cancer. Of note, a key study on urothelial progenitor cells recently highlighted an important role for Sonic hedgehog-positive cells and retinoid signaling that is essential for urothelial development and regeneration. In the translational realm, transgenic mouse models continue to be used, with a recent interest in the role of Wnt/beta-catenin in urothelial carcinomas. Tissue recombination models are also being increasingly utilized to better recreate the tissue microenvironment and better understand stromal-epithelial interactions and the impact of genetic alterations on tissue differentiation. Lastly, the avatar mouse systems, which involve direct xenotransplantation of human tumor specimens into immunocompromised mice, represent an additional approach to study cancer characteristics in a preserved tissue context.
SUMMARY - With molecular alterations remaining an unclear area of our understanding of HR-NMIBC, preclinical models of bladder cancer serve as essential tools to discover specific genetic compromises in disease pathogenesis and the therapeutics to treat them.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Smad6 suppresses the growth and self-renewal of hepatic progenitor cells.
Ding ZY, Liang HF, Jin GN, Chen WX, Wang W, Datta PK, Zhang MZ, Zhang B, Chen XP
(2014) J Cell Physiol 229: 651-60
MeSH Terms: Animals, Cell Line, Cell Proliferation, Gene Expression Regulation, Liver, Liver Regeneration, Rats, Smad6 Protein, Stem Cells, Wnt Signaling Pathway, beta Catenin
Show Abstract · Added February 26, 2014
Activation of hepatic progenitor cells (HPCs) is commonly observed in chronic liver disease and Wnt/β-catenin signaling plays a crucial role in the expansion of HPCs. However, the molecular mechanisms that regulate the activation of Wnt/β-catenin signaling in the liver, especially in HPCs, remain largely elusive. Here, we reported that ectopic expression of Smad6 suppressed the proliferation and self-renewal of WB-F344 cells, a HPC cell line. Mechanistically, we found that Smad6 inhibited Wnt/β-catenin signaling through promoting the interaction of C-terminal binding protein (CtBP) with β-catenin/T-cell factor (TCF) complex to inhibit β-catenin mediated transcriptional activation in WB-F344 cells. We used siRNA targeting β-catenin to demonstrate that Wnt/β-catenin signaling was required for the proliferation and self-renewal of HPCs. Taken together, these results suggest that Smad6 is a regulatory molecule which regulates the proliferation, self-renewal and Wnt/β-catenin signaling in HPCs.
© 2013 Wiley Periodicals, Inc.
1 Communities
1 Members
0 Resources
11 MeSH Terms