scholarly journals Attachment of Cancer Urothelial Cells to the Bladder Epithelium Occurs on Uroplakin-Negative Cells and Is Mediated by Desmosomal and Not by Classical Cadherins

2021 ◽  
Vol 22 (11) ◽  
pp. 5565
Author(s):  
Urška Dragin Jerman ◽  
Tanja Višnjar ◽  
Iva Hafner Bratkovič ◽  
Nataša Resnik ◽  
Mojca Pavlin ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cancer Cells ◽  
Urothelial Cancer ◽  
Urinary Bladder Cancer ◽  
Urothelial Cells ◽  
Bladder Epithelium ◽  
T24 Cells ◽  
Classical Cadherins ◽  
E Cadherin

Urinary bladder cancer is often multifocal; however, the intraluminal dissemination of the urothelial cancer cells is poorly understood. The involvement of N-cadherin in the adhesion of the cancer urothelial cells to the urothelium had not previously been studied. Therefore, we herein explore the possibility of the intraluminal dissemination of the urothelial cancer cells by evaluating the role of classical cadherins in the adhesion of urothelial cancer cells to the urothelium. We used E-cadherin negative T24 cells and established a T24 Ncadlow cell line with an additionally decreased expression of N-cadherin in the plasma membrane and a decreased secretion of proform of metalloproteinase 2. The labelled T24 and T24 Ncadlow cells were seeded onto urothelial in vitro models. After 24 h in co-culture, unattached cancer cells were rinsed and urothelia with attached cancer urothelial cells were processed for fluorescence and electron microscopy. Both the T24 and T24 Ncadlow cells attached to the urothelium, yet only to the uroplakin-negative urothelial cells. The ultrastructural analysis showed that T24 and T24 Ncadlow cells adhere to poorly differentiated urothelial cells by desmosomes. To achieve this, they first disrupt tight junctions of superficial urothelial cells. This study indicates that the lack of E-cadherin expression and decreased expression of N-cadherin in the plasma membrane of T24 cells does not interfere with their adhesion to the urothelium; therefore, our results suggest that intraluminal dissemination of cancer urothelial cells along the urothelium occurs on uroplakin-negative cells and is desmosome-mediated.

scholarly journals E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway

2012 ◽  
Vol 33 (6) ◽  
pp. 817-822 ◽  
Author(s):  
Ling-ling Dong ◽  
Lian Liu ◽  
Chun-hong Ma ◽  
Ji-sheng Li ◽  
Chao Du ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Erk Pathway ◽  
E Cadherin

Dominant-negative E-cadherin inhibits the invasiveness of inflammatory breast cancer cells in vitro

2006 ◽  
Vol 133 (2) ◽  
pp. 83-92 ◽  
Author(s):  
Hui-Ming Dong ◽  
Gang Liu ◽  
Yi-Feng Hou ◽  
Jiong Wu ◽  
Jin-Song Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Inflammatory Breast Cancer ◽  
Breast Cancer Cells ◽  
Dominant Negative ◽  
E Cadherin

scholarly journals NRF2 activates a partial epithelial-mesenchymal transition and is maximally present in a hybrid epithelial/mesenchymal phenotype

2019 ◽  
Vol 11 (6) ◽  
pp. 251-263 ◽  
Author(s):  
Federico Bocci ◽  
Satyendra C Tripathi ◽  
Samuel A Vilchez Mercedes ◽  
Jason T George ◽  
Julian P Casabar ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Collective Cell Migration ◽  
Mesenchymal Transition ◽  
Regulatory Circuit ◽  
Clinical Records ◽  
E Cadherin

Abstract The epithelial-mesenchymal transition (EMT) is a key process implicated in cancer metastasis and therapy resistance. Recent studies have emphasized that cells can undergo partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype – a cornerstone of tumour aggressiveness and poor prognosis. These cells can have enhanced tumour-initiation potential as compared to purely epithelial or mesenchymal ones and can integrate the properties of cell-cell adhesion and motility that facilitates collective cell migration leading to clusters of circulating tumour cells (CTCs) – the prevalent mode of metastasis. Thus, identifying the molecular players that can enable cells to maintain a hybrid E/M phenotype is crucial to curb the metastatic load. Using an integrated computational-experimental approach, we show that the transcription factor NRF2 can prevent a complete EMT and instead stabilize a hybrid E/M phenotype. Knockdown of NRF2 in hybrid E/M non-small cell lung cancer cells H1975 and bladder cancer cells RT4 destabilized a hybrid E/M phenotype and compromised the ability to collectively migrate to close a wound in vitro. Notably, while NRF2 knockout simultaneously downregulated E-cadherin and ZEB-1, overexpression of NRF2 enriched for a hybrid E/M phenotype by simultaneously upregulating both E-cadherin and ZEB-1 in individual RT4 cells. Further, we predict that NRF2 is maximally expressed in hybrid E/M phenotype(s) and demonstrate that this biphasic dynamic arises from the interconnections among NRF2 and the EMT regulatory circuit. Finally, clinical records from multiple datasets suggest a correlation between a hybrid E/M phenotype, high levels of NRF2 and its targets and poor survival, further strengthening the emerging notion that hybrid E/M phenotype(s) may occupy the ‘metastatic sweet spot’.

scholarly journals The plasma membrane transporter SLC5A8 suppresses tumour progression through depletion of survivin without involving its transport function

2013 ◽  
Vol 450 (1) ◽  
pp. 169-178 ◽  
Author(s):  
Veena Coothankandaswamy ◽  
Selvakumar Elangovan ◽  
Nagendra Singh ◽  
Puttur D. Prasad ◽  
Muthusamy Thangaraju ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cancer Cells ◽  
Histone Deacetylase Inhibitors ◽  
Tumour Progression ◽  
Ectopic Expression ◽  
Membrane Transporter ◽  
Transport Function ◽  
Plasma Membrane Transporter

SLC5A8 (solute carrier gene family 5A, member 8) is a sodium-coupled transporter for monocarboxylates. Among its substrates are the HDAC (histone deacetylase) inhibitors butyrate, propionate and pyruvate. Expression of SLC5A8 is silenced in cancers via DNA methylation, and ectopic expression of SLC5A8 in cancer cells induces apoptosis in the presence of its substrates that are HDAC inhibitors. In the present study we show that ectopic expression of SLC5A8 in cancer cells translocates the anti-apoptotic protein survivin to the plasma membrane through protein–protein interaction resulting in depletion of nuclear survivin and also decreases cellular levels of survivin through inhibition of transcription. These SLC5A8-induced changes in the location and levels of survivin result in cell-cycle arrest, disruption of the chromosome passenger complex involved in mitosis, induction of apoptosis and enhancement in chemosensitivity. These effects are seen independently of the transport function of SLC5A8 and histone acetylation status of the cell; in the presence of pyruvate, a SLC5A8 substrate and also an HDAC inhibitor, these effects are amplified. Ectopic expression of SLC5A8 in the breast cancer cell line MB231 inhibits the ability of cells to form colonies in vitro and to form tumours in mouse xenografts in vivo. The suppression of survivin transcription occurs independently of HDAC inhibition, and the underlying mechanism is associated with decreased phosphorylation of STAT3 (signal transducer and activator of transcription 3). The observed effects are specific for survivin with no apparent changes in expression of other inhibitor-of-apoptosis proteins. The present study unravels a novel, hitherto unrecognized, mechanism for the tumour-suppressive role of a plasma membrane transporter independent of its transport function.

scholarly journals Combined cytotoxic effect of UV-irradiation and TiO2microbeads in normal urothelial cells, low-grade and high-grade urothelial cancer cells

2015 ◽  
Vol 14 (3) ◽  
pp. 583-590 ◽  
Author(s):  
Roghayeh Imani ◽  
Peter Veranič ◽  
Aleš Iglič ◽  
Mateja Erdani Kreft ◽  
Meysam Pazoki ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Uv Irradiation ◽  
Cytotoxic Effect ◽  
Urothelial Cancer ◽  
Low Grade ◽  
High Grade ◽  
Urothelial Cells ◽  
Efficient Approach

Paper shows that internalization of the TiO2microbeads followed by the UV-irradiation is an efficient approach for killing cancer urothelial cells. Additionally, differentiation dependent differences in the sensitivity of the cells to the UV-irradiation are shown, and a model of photocatalytic treatment of thein vivobladder cancer is presented.

scholarly journals Levels of Soluble E-Cadherin in Breast, Gastric, and Colorectal Cancers

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ombretta Repetto ◽  
Paolo De Paoli ◽  
Valli De Re ◽  
Vincenzo Canzonieri ◽  
Renato Cannizzaro
Keyword(s):  
Cell Adhesion ◽  
Cancer Cells ◽  
Body Fluids ◽  
Colorectal Cancers ◽  
Protein Fragment ◽  
Epithelial Cadherin ◽  
Cancer Dynamics ◽  
E Cadherin

Soluble E-cadherin is a 80 kDa protein fragment coming from the proteolytic cleavage of the extracellular domain of the full length epithelial cadherin, a molecule involved in cell adhesion/polarity and tissue morphogenesis. In comparison with normal epithelia, cancer cells show a decreased cadherin-mediated intercellular adhesion, and sE-cad levels normally increase in body fluids (blood and urine). This review focuses on soluble E-cadherin in sera of patients affected by three solid cancers (breast, gastric, and colorectal cancers) and how its levels correlate or not with some cancer parameters (e.g., dimension, progression, and localisation). We will describe the main proteomics approaches adopted to measure sE-cad bothin vivoandin vitroand the most important findings about its behaviour in cancer dynamics.

Assembly of the cadherin-catenin complex in vitro with recombinant proteins

1994 ◽  
Vol 107 (12) ◽  
pp. 3655-3663 ◽  
Author(s):  
H. Aberle ◽  
S. Butz ◽  
J. Stappert ◽  
H. Weissig ◽  
R. Kemler ◽  
...  
Keyword(s):  
Cytoplasmic Domain ◽  
Beta Catenin ◽  
Molecular Architecture ◽  
Adhesive Properties ◽  
Protein Protein Interaction ◽  
Signalling Molecules ◽  
Classical Cadherins ◽  
E Cadherin

The cytoplasmic domain of classical cadherins is tightly associated with three proteins termed alpha-, beta- and gamma-catenin. These accessory proteins are of central importance for the adhesive properties of this class of cell adhesion molecules. In order to examine the molecular architecture of the cadherin-catenin complex in more detail we have expressed the catenins and the cytoplasmic domain of E-cadherin as fusion proteins in Escherichia coli, and analyzed the interaction of purified recombinant cadherin and catenins in combinatorial protein-protein interaction experiments. The cytoplasmic domain of E-cadherin cannot directly associate with alpha-catenin but interacts with high affinity with beta-catenin, whereas the binding of gamma-catenin (plakoglobin) to E-cadherin is less efficient. alpha- and beta-catenin assemble into a 1:1 heterodimeric complex. The analysis of various truncated beta-catenins revealed that an alpha-catenin binding site in beta-catenin is localized between amino acid positions 120 and 151. The central role of beta-catenin for the assembly of the heterotrimeric E-cadherin/alpha-catenin/beta-catenin complex in mixing experiments with all components was demonstrated. The reconstitution in vitro of the cadherin-catenin complex should allow the study of the interaction with signalling molecules and with the actin-based cytoskeleton.

scholarly journals Phosphoprotein Phosphatase 1 Is Required for Extracellular Calcium-Induced Keratinocyte Differentiation

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Chandrama Shrestha ◽  
Yuanyuan Tang ◽  
Hong Fan ◽  
Lusha Li ◽  
Qin Zeng ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Second Messengers ◽  
Human Keratinocytes ◽  
Extracellular Calcium ◽  
Keratinocyte Differentiation ◽  
Differentiation Markers ◽  
Calcium Stimulation ◽  
E Cadherin

Extracellular calcium is a major regulator of keratinocyte differentiation in vitro and appears to play that role in vivo, but the mechanism is unclear. We have previously demonstrated that, following calcium stimulation, PIP5K1αis recruited by the E-cadherin-β-catenin complex to the plasma membrane where it provides the substrate PIP2 for both PI3K and PLC-γ1. This signaling pathway is critical for calcium-induced generation of second messengers including IP3 and intracellular calcium and keratinocyte differentiation. In this study, we explored the upstream regulatory mechanism by which calcium activates PIP5K1αand the role of this activation in calcium-induced keratinocyte differentiation. We found that treatment of human keratinocytes in culture with calcium resulted in an increase in serine dephosphorylation and PIP5K1αactivation. PP1 knockdown blocked extracellular calcium-induced increase in serine dephosphorylation and activity of PIP5K1αand induction of keratinocyte differentiation markers. Knockdown of PLC-γ1, the downstream effector of PIP5K1α, blocked upstream dephosphorylation and PIP5K1αactivation induced by calcium. Coimmunoprecipitation revealed calcium induced recruitment of PP1 to the E-cadherin-catenin-PIP5K1αcomplex in the plasma membrane. These results indicate that PP1 is recruited to the extracellular calcium-dependent E-cadherin-catenin-PIP5K1αcomplex in the plasma membrane to activate PIP5K1α, which is required for PLC-γ1 activation leading to keratinocyte differentiation.

scholarly journals ZEB1 Enhances Transendothelial Migration and Represses the Epithelial Phenotype of Prostate Cancer Cells

2009 ◽  
Vol 20 (8) ◽  
pp. 2207-2217 ◽  
Author(s):  
Justin M. Drake ◽  
Garth Strohbehn ◽  
Thomas B. Bair ◽  
Jessica G. Moreland ◽  
Michael D. Henry
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Transendothelial Migration ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition ◽  
Metastatic Colonization ◽  
E Cadherin

Metastatic colonization involves cancer cell lodgment or adherence in the microvasculature and subsequent migration of those cells across the endothelium into a secondary organ site. To study this process further, we analyzed transendothelial migration of human PC-3 prostate cancer cells in vitro. We isolated a subpopulation of cells, TEM4-18, that crossed an endothelial barrier more efficiently, but surprisingly, were less invasive than parental PC-3 cells in other contexts in vitro. Importantly, TEM4-18 cells were more aggressive than PC-3 cells in a murine metastatic colonization model. Microarray and FACS analysis of these cells showed that the expression of many genes previously associated with leukocyte trafficking and cancer cell extravasation were either unchanged or down-regulated. Instead, TEM4-18 cells exhibited characteristic molecular markers of an epithelial-to-mesenchymal transition (EMT), including frank loss of E-cadherin expression and up-regulation of the E-cadherin repressor ZEB1. Silencing ZEB1 in TEM4-18 cells resulted in increased E-cadherin and reduced transendothelial migration. TEM4-18 cells also express N-cadherin, which was found to be necessary, but not sufficient for increased transendothelial migration. Our results extend the role of EMT in metastasis to transendothelial migration and implicate ZEB1 and N-cadherin in this process in prostate cancer cells.

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