scholarly journals Claudin Family of Proteins and Cancer: An Overview

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Amar B. Singh ◽  
Ashok Sharma ◽  
Punita Dhawan
Keyword(s):  
Cell Adhesion ◽  
Tight Junction ◽  
Tight Junctions ◽  
Apical Cell ◽  
Cellular Transformation ◽  
Molecular Architecture ◽  
Human Carcinoma ◽  
Potential Implication ◽  
Cell Cell

Tight junctions are the apical cell-cell adhesion that regulate paracellular permeability and are critical for epithelial cell polarity. Molecular architecture of tight junction has been studied extensively, which has confirmed that claudin family of proteins is integral component of tight junction. Loss of cell-cell adhesion is central to the cellular transformation and acquisition of metastatic potential; however, the role of claudin family of proteins play in a series of pathophysiological events, including human carcinoma development, is only now beginning to be understood. Several claudin mouse knockout models have been generated and the diversity of phenotypes observed clearly demonstrates their important roles in the maintenance of tissue integrity in various organs and suggest that claudins also participate in cellular contexts other than tight junctions. The mechanisms of claudin regulation and their exact roles in normal physiology and disease are being elucidated, but much work remains to be done. In this review, we have discussed the conceptual framework concerning claudins and their potential implication in cancer. We predict that next several years will likely witness a boom in our understanding of the potential role of claudins in the regulation of tumorigenesis, which may, in turn, provide new approaches for the targeted therapy.

scholarly journals Role of Claudin Proteins in Regulating Cancer Stem Cells and Chemoresistance-Potential Implication in Disease Prognosis and Therapy

2019 ◽  
Vol 21 (1) ◽  
pp. 53 ◽  
Author(s):  
Saiprasad Gowrikumar ◽  
Amar B. Singh ◽  
Punita Dhawan
Keyword(s):  
Stem Cells ◽  
Cell Adhesion ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Therapy Resistance ◽  
Cell Phenotype ◽  
Potential Implication ◽  
Mesenchymal Transition ◽  
Cell Cell

Claudins are cell–cell adhesion proteins, which are expressed in tight junctions (TJs), the most common apical cell-cell adhesion. Claudin proteins help to regulate defense and barrier functions, as well as differentiation and polarity in epithelial and endothelial cells. A series of studies have now reported dysregulation of claudin proteins in cancers. However, the precise mechanisms are still not well understood. Nonetheless, studies have clearly demonstrated a causal role of multiple claudins in the regulation of epithelial to mesenchymal transition (EMT), a key feature in the acquisition of a cancer stem cell phenotype in cancer cells. In addition, claudin proteins are known to modulate therapy resistance in cancer cells, a feature associated with cancer stem cells. In this review, we have focused primarily on highlighting the causal link between claudins, cancer stem cells, and therapy resistance. We have also contemplated the significance of claudins as novel targets in improving the efficacy of cancer therapy. Overall, this review provides a much-needed understanding of the emerging role of claudin proteins in cancer malignancy and therapeutic management.

scholarly journals Novel role of nectin: implication in the co-localization of JAM-A and claudin-1 at the same cell-cell adhesion membrane domain

2008 ◽  
Vol 13 (8) ◽  
pp. 797-805 ◽  
Author(s):  
Kaori Kuramitsu ◽  
Wataru Ikeda ◽  
Naoya Inoue ◽  
Yoshiyuki Tamaru ◽  
Yoshimi Takai
Keyword(s):  
Cell Adhesion ◽  
Membrane Domain ◽  
Cell Cell

scholarly journals Rab13 regulates PKA signaling during tight junction assembly

2004 ◽  
Vol 165 (2) ◽  
pp. 175-180 ◽  
Author(s):  
Katja Köhler ◽  
Daniel Louvard ◽  
Ahmed Zahraoui
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
Inhibitory Effect ◽  
Cell Junctions ◽  
Unknown Mechanism ◽  
Epithelial Tight Junctions ◽  
Actin Remodelling ◽  
Cell Cell

The GTPase Rab13 regulates the assembly of functional epithelial tight junctions (TJs) through a yet unknown mechanism. Here, we show that expression of the GTP-bound form of Rab13 inhibits PKA-dependent phosphorylation and TJ recruitment of the vasodilator-stimulated phosphoprotein, an actin remodelling protein. We demonstrate that Rab13GTP directly binds to PKA and inhibits its activity. Interestingly, activation of PKA abrogates the inhibitory effect of Rab13 on the recruitment of vasodilator-stimulated phosphoprotein, ZO-1, and claudin1 to cell–cell junctions. Rab13 is, therefore, the first GTPase that controls PKA activity and provides an unexpected link between PKA signaling and the dynamics of TJ assembly.

scholarly journals Combining experiments and in silico modeling to infer the role of adhesion and proliferation on the collective dynamics of cells

2021 ◽  
Author(s):  
Hygor P. M. Melo ◽  
F. Raquel Maia ◽  
André S. Nunes ◽  
Rui L. Reis ◽  
Joaquim M. Oliveira ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Adhesion ◽  
Glioblastoma Multiforme ◽  
In Silico ◽  
Relative Importance ◽  
Collective Dynamics ◽  
Surfaces And Interfaces ◽  
In Silico Modeling ◽  
Cell Cell

ABSTRACTThe collective dynamics of cells on surfaces and interfaces poses technological and theoretical challenges in the study of morphogenesis, tissue engineering, and cancer. Different mechanisms are at play, including, cell-cell adhesion, cell motility, and proliferation. However, the relative importance of each one is elusive. Here, experiments with a culture of glioblastoma multiforme cells on a substrate are combined with in silico modeling to infer the rate of each mechanism. By parametrizing these rates, the time-dependence of the spatial correlation observed experimentally is reproduced. The obtained results suggest a reduction in cell-cell adhesion with the density of cells. The reason for such reduction and possible implications for the collective dynamics of cancer cells are discussed.

scholarly journals CUL4A ubiquitin ligase: a promising drug target for cancer and other human diseases

Open Biology ◽  
2014 ◽  
Vol 4 (2) ◽  
pp. 130217 ◽  
Author(s):  
Puneet Sharma ◽  
Alo Nag
Keyword(s):  
Ubiquitin Ligase ◽  
Drug Target ◽  
Critical Role ◽  
Cellular Transformation ◽  
Biological Processes ◽  
Molecular Architecture ◽  
The Past ◽  
Cullin 4A ◽  
Broad Overview

The ability of cullin 4A (CUL4A), a scaffold protein, to recruit a repertoire of substrate adaptors allows it to assemble into distinct E3 ligase complexes to mediate turnover of key regulatory proteins. In the past decade, a considerable wealth of information has been generated regarding its biology, regulation, assembly, molecular architecture and novel functions. Importantly, unravelling of its association with multiple tumours and modulation by viral proteins establishes it as one of the key proteins that may play an important role in cellular transformation. Considering the role of its substrate in regulating the cell cycle and maintenance of genomic stability, understanding the detailed aspects of these processes will have significant consequences for the treatment of cancer and related diseases. This review is an effort to provide a broad overview of this multifaceted ubiquitin ligase and addresses its critical role in regulation of important biological processes. More importantly, its tremendous potential to be exploited for therapeutic purposes has been discussed.

Role of the second immunoglobulin-like loop of nectin in cell–cell adhesion

2002 ◽  
Vol 293 (1) ◽  
pp. 45-49 ◽  
Author(s):  
Yumiko Momose ◽  
Tomoyuki Honda ◽  
Maiko Inagaki ◽  
Kazuya Shimizu ◽  
Kenji Irie ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Cell

Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis. I. Lung epithelial morphogenesis

Development ◽  
1989 ◽  
Vol 105 (2) ◽  
pp. 263-270 ◽  
Author(s):  
Y. Hirai ◽  
A. Nose ◽  
S. Kobayashi ◽  
M. Takeichi
Keyword(s):  
Monoclonal Antibody ◽  
Cell Adhesion ◽  
Epithelial Cells ◽  
Adhesion Molecules ◽  
Lung Epithelial Cells ◽  
Early Developmental Stage ◽  
Subtle Effect ◽  
Lung Epithelial ◽  
Cell Cell

The role of Ca2+-dependent cell-cell adhesion molecules, E- and P-cadherins, in the histogenesis of mouse embryonic lung was studied. All epithelial cells of the lung express both E- and P-cadherin at the early developmental stage. P-cadherin, however, gradually disappears during development, initially from the main bronchi and eventually from all epithelial cells. When a monoclonal antibody to E-cadherin (ECCD-1) was added to monolayer cultures of lung epithelial cells, it induced a partial disruption of their cell-cell adhesion, while a monoclonal antibody to P-cadherin (PCD-1) showed a subtle effect. A mixture of the two antibodies, however, displayed a synergistic effect. We then tested the effect of the antibodies on the morphogenesis of lung primordia using an organ culture system. In control media, the explants formed typical bronchial trees. In the presence of ECCD-1, the explants grew up at the same rate as in the control, but their morphogenesis was affected. The control explants formed round epithelial lobules with an open luminal space at the tips of the bronchial trees, whereas the lobules of explants incubated with ECCD-1 tended to be flat and devoid of the luminal space. PCD-1 showed a similar but very small effect. A mixture of the two antibodies, however, showed a stronger effect: the branching of epithelia was partially suppressed and the arrangement of epithelial cells was distorted in many places. These results suggest that E- and P-cadherin have a synergistic role in the organization of epithelial cells in lung morphogenesis.

Abstract 361: Creg1 Interacts With Sec8 to Promote Cell-cell Adhesion During Cardiomyogenesis

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Jie Liu ◽  
Yanmei Qi ◽  
Shu-Chan Hsu ◽  
Siavash Saadat ◽  
Saum Rahimi ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Es Cells ◽  
Embryonic Stem ◽  
Intercellular Junctions ◽  
Amino Acid Residues ◽  
Loss Of Function ◽  
Wild Type ◽  
Adhesion Sites ◽  
Cell Cell

Cellular repressor of E1A-stimulated genes 1 (CREG1) is a 24 kD glycoprotein essential for early embryonic development. Our immunofluorescence studies revealed that CREG1 is highly expressed at myocyte junctions in both embryonic and adult hearts. To explore it role in cardiomyogenesis, we employed gain- and loss-of-function analyses demonstrating that CREG1 is required for the differentiation of mouse embryonic stem (ES) cell into cohesive myocardium-like structures. Chimeric cultures of wild-type and CREG1 knockout ES cells expressing cardiac-specific reporters showed that the cardiomyogenic effect of CREG1 is cell autonomous. Furthermore, we identified a novel interaction between CREG1 and Sec8 of the exocyst complex, which tethers vesicles to the plasma membrane. Mutations of the amino acid residues D141 and P142 to alanine in CREG1 abolished its binding to Sec8. To address the role of the CREG1-Sec8 interaction in cardiomyogenesis, we rescued CREG1 knockout ES cells with wild-type and Sec8-binding mutant CREG1 and showed that CREG1 binding to Sec8 promotes cardiomyocyte differentiation and cohesion. Mechanistically, CREG1, Sec8 and N-cadherin all localize at cell-cell adhesion sites. CREG1 overexpression enhances the assembly of adherens and gap junctions. By contrast, its knockout inhibits the Sec8-N-cadherin interaction and induces their degradation. Finally, shRNA-mediated knockdown of Sec8 leads to cardiomyogenic defects similar to CREG1 knockout. These results suggest that the CREG1 binding to Sec8 enhances the assembly of intercellular junctions and promotes cardiomyogenesis.

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