scholarly journals Facets of Communication: Gap Junction Ultrastructure and Function in Cancer Stem Cells and Tumor Cells

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 288 ◽  
Author(s):  
Anja Beckmann ◽  
Nadine Hainz ◽  
Thomas Tschernig ◽  
Carola Meier
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Gap Junctions ◽  
Gap Junction ◽  
Cancer Cells ◽  
Freeze Fracture ◽  
Plaque Morphology ◽  
Junctional Communication ◽  
Gap Junction Proteins ◽  
Junction Proteins

Gap junction proteins are expressed in cancer stem cells and non-stem cancer cells of many tumors. As the morphology and assembly of gap junction channels are crucial for their function in intercellular communication, one focus of our review is to outline the data on gap junction plaque morphology available for cancer cells. Electron microscopic studies and freeze-fracture analyses on gap junction ultrastructure in cancer are summarized. As the presence of gap junctions is relevant in solid tumors, we exemplarily outline their role in glioblastomas and in breast cancer. These were also shown to contain cancer stem cells, which are an essential cause of tumor onset and of tumor transmission into metastases. For these processes, gap junctional communication was shown to be important and thus we summarize, how the expression of gap junction proteins and the resulting communication between cancer stem cells and their surrounding cells contributes to the dissemination of cancer stem cells via blood or lymphatic vessels. Based on their importance for tumors and metastases, future cancer-specific therapies are expected to address gap junction proteins. In turn, gap junctions also seem to contribute to the unattainability of cancer stem cells by certain treatments and might thus contribute to therapeutic resistance.

Synthesis and assembly of human beta 1 gap junctions in BHK cells by DNA transfection with the human beta 1 cDNA

1995 ◽  
Vol 108 (12) ◽  
pp. 3725-3734 ◽  
Author(s):  
N.M. Kumar ◽  
D.S. Friend ◽  
N.B. Gilula
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Freeze Fracture ◽  
Growth Control ◽  
Double Membrane ◽  
Correct Orientation ◽  
Junctional Communication ◽  
Junction Protein ◽  
Particle Aggregates ◽  
Metallothionein Promoter

Gap junctional communication is important in many physiological processes, including growth control, patterning, and the synchronization of cell-to-cell activities. It has been difficult to study the synthesis and assembly of gap junctions due to their low abundance. To overcome this limitation, baby hamster kidney cells (BHK) have been transfected with a human beta 1 (Cx32) connexin cDNA construct. Expression was placed under the control of the mouse metallothionein promoter that can be induced by heavy metals. The transfected cells were characterized by DNA, RNA and protein analysis, as well as by scrape loading to detect functional channels. Functional beta 1 connexin was detected only in cells transfected with beta 1 connexin cDNA in the correct orientation (beta 1-BHK). Analysis of the cells by light microscopic immunocytochemistry indicated that beta 1 connexin antigen was localized to the plasma membrane and to several intracellular compartments. Characterization with thin section electron microscopy revealed extensive areas of assembled double membrane gap junctions between cells (on the cell surface), in the endoplasmic reticulum (ER), and the nuclear envelope. This unusual intracellular distribution for assembled gap junction protein was confirmed by freeze fracture analysis, which revealed large particle aggregates, characteristic of gap junction plaques, on the fracture faces of all these membranes. The presence of gap junction particle aggregates in the ER suggests that the oligomerization of connexin can occur at its site of synthesis. Further, the process of assembly into double membrane junction structures in intracellular membranes may be driven by connexin protein concentration.

scholarly journals βPS-Integrin acts downstream of Innexin 2 in modulating stretched cell morphogenesis in the Drosophila ovary

2021 ◽  
Author(s):  
Yi-Chia Huang ◽  
Kuan-Han Chen ◽  
Yu-Yang Chen ◽  
Liang-Hsuan Tsao ◽  
Tsung-Han Yeh ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Adaptor Proteins ◽  
Follicle Cells ◽  
Cell Morphogenesis ◽  
Independent Manner ◽  
Gap Junction Proteins ◽  
Intercellular Exchange ◽  
Drosophila Ovary ◽  
Junction Proteins

Abstract During oogenesis, a group of specialized follicle cells, known as stretched cells, flatten drastically from cuboidal to squamous shape. While morphogenesis of epithelia is critical for organogenesis, genes and signaling pathways involved in this process remain to be revealed. In addition to formation of gap junctions for intercellular exchange of small molecules, gap junction proteins form channels or act as adaptor proteins to regulate various cellular behaviors. In invertebrates, gap junction proteins are Innexins. Knockdown of Innexin 2 but not other Innexins expressed in follicle cells attenuates stretched cell morphogenesis. Interestingly, blocking of gap junctions with an inhibitor carbenoxolone does not affect stretched cell morphogenesis, suggesting that Innexin 2 might control stretched cell flattening in a gap-junction-independent manner. An excessive level of βPS-Integrin encoded by myospheroid is detected in Innexin 2 mutant cells specifically during stretched cell morphogenesis. Simultaneous knockdown of Innexin 2 and myospheroid partially rescues the morphogenetic defect resulted from Innexin 2 knockdown. Furthermore, reduction of βPS-Integrin is sufficient to induce early stretched cell flattening. Taken together, our data suggest that βPS-Integrin acts downstream of Innexin 2 in modulating stretched cell morphogenesis.

scholarly journals Analyzing phorbol ester effects on gap junctional communication: a dramatic inhibition of assembly.

1994 ◽  
Vol 127 (6) ◽  
pp. 1895-1905 ◽  
Author(s):  
P D Lampe
Keyword(s):  
Plasma Membrane ◽  
Gap Junctions ◽  
Gap Junction ◽  
Lucifer Yellow ◽  
Single Cells ◽  
Freeze Fracture ◽  
Dye Transfer ◽  
Novikoff Hepatoma ◽  
Junctional Communication ◽  
Junction Protein

The effect of 12-O-tetradeconylphorbol-13-acetate (TPA) on gap junction assembly between Novikoff hepatoma cells was examined. Cells were dissociated with EDTA to single cells and then reaggregated to form new junctions. When TPA (25 nM) was added to the cells at the onset of the 60-min reaggregation, dye transfer was detected at only 0.6% of the cell-cell interfaces compared to 72% for the untreated control and 74% for 4-alpha TPA, an inactive isomer of TPA. Freeze-fracture electron microscopy of reaggregated control cells showed interfaces containing an average of more than 600 aggregated intramembranous gap junction particles, while TPA-treated cells had no gap junctions. However, Lucifer yellow dye transfer between nondissociated cells via gap junctions was unaffected by 60 min of TPA treatment. Therefore, TPA dramatically inhibited gap junction assembly but did not alter channel gating nor enhance disassembly of preexisting gap junction structures. Short term TPA treatment (< 30 min) increased phosphorylation of the gap junction protein molecular weight of 43,000 (Cx43), but did not change the cellular level of Cx43. Cell surface biotinylation experiments suggested that TPA did not substantially reduce the plasma membrane concentration of Cx43. Therefore, the simple presence of Cx43 in the plasma membrane is not sufficient for gap junction assembly, and protein kinase C probably exerts an effect on assembly of gap junctions at the plasma membrane level.

Targeting Cancer Stem Cells and Non-Stem Cancer Cells: The Potential of Lipid- Based Nanoparticles

2018 ◽  
Vol 23 (43) ◽  
pp. 6563-6572
Author(s):  
Ana Filipa Cruz ◽  
Nuno Andre Fonseca ◽  
Vera Moura ◽  
Sergio Simoes ◽  
Joao Nuno Moreira
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells

Comparison of the Growth Curves of Cancer Cells and Cancer Stem Cells

2014 ◽  
Vol 9 (2) ◽  
pp. 112-116 ◽  
Author(s):  
Maria Toloudi ◽  
Eleni Ioannou ◽  
Marina Chatziioannou ◽  
Panagiotis Apostolou ◽  
Christos Kiritsis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Growth Curves

Resveratrol as an Enhancer of Apoptosis in Cancer: A Mechanistic Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Shahram Taeb ◽  
Hamed Haghi-Aminjan ◽  
Shima Afrashi ◽  
Kave Moloudi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Fas Ligand ◽  
Inhibitory Effect ◽  
Mitochondrial Pathway ◽  
Multi Drug Resistance ◽  
Chemotherapy Drugs ◽  
Normal Tissues ◽  
Anti Cancer

: Resistance of cancer cells to therapy is a challenge for achieving an appropriate therapeutic outcome. Cancer (stem) cells possess several mechanisms for increasing their survival following exposure to toxic agents such as chemotherapy drugs, radiation as well as immunotherapy. Evidences show that apoptosis plays a key role in response of cancer (stem) cells and their multi drug resistance. Modulation of both intrinsic and extrinsic pathways of apoptosis can increase efficiency of tumor response and amplify the therapeutic effect of radiotherapy, chemotherapy, targeted therapy and also immunotherapy. To date, several agents as adjuvant have been proposed to overcome resistance of cancer cells to apoptosis. Natural products are interesting because of low toxicity on normal tissues. Resveratrol is a natural herbal agent that has shown interesting anti-cancer properties. It has been shown to kill cancer cells selectively, while protecting normal cells. Resveratrol can augment reduction/oxidation (redox) reactions, thus increases the production of ceramide and the expression of apoptosis receptors such as Fas ligand (FasL). Resveratrol also triggers some pathways which induce mitochondrial pathway of apoptosis. On the other hand, resveratrol has an inhibitory effect on anti-apoptotic mediators such as nuclear factor κ B (NFκB), cyclooxygenase-2 (COX-2), phosphatidylinositol 3–kinase (PI3K) and mTOR. In this review, we explain the modulatory effects of resveratrol on apoptosis, which can augment the therapeutic efficiency of anti-cancer drugs or radiotherapy.

scholarly journals The microRNA-210-Stathmin1 Axis Decreases Cell Stiffness to Facilitate the Invasiveness of Colorectal Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1833
Author(s):  
Tsai-Tsen Liao ◽  
Wei-Chung Cheng ◽  
Chih-Yung Yang ◽  
Yin-Quan Chen ◽  
Shu-Han Su ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Motility ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Stiffness ◽  
Mesenchymal Transition ◽  
Cytoskeletal Dynamics ◽  
Colorectal Cancer Stem Cells

Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

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