scholarly journals Keratin 19 maintains E-cadherin localization at the cell surface and stabilizes cell-cell adhesion of MCF7 cells

2020 ◽  
Author(s):  
Sarah Alsharif ◽  
Pooja Sharma ◽  
Karina Bursch ◽  
Rachel Milliken ◽  
Meagan Collins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Cell Mechanics ◽  
Mcf7 Cells ◽  
Growth And Survival ◽  
Recycling Endosomes ◽  
Keratin 19 ◽  
E Cadherin ◽  
Cell Cell

AbstractA cytoskeletal protein keratin 19 (K19) is highly expressed in breast cancer but its effects on breast cancer cell mechanics are unclear. Using KRT19 knockout (KO) cells and cells where K19 expression was rescued, we found that K19 is required to maintain rounded epithelial-like shape and tight cell-cell adhesion of MCF7 cells. A loss of K19 resulted in a lower level of plakoglobin and internalization of E-cadherin in early and recycling endosomes. Inhibiting internalization restored cell-cell adhesion of KRT19 KO cells, suggesting E-cadherin internalization contributes to defective adhesion. Ultimately, while K19 inhibited cell migration, it was required for cells to form colonies in suspension. Our results suggest that K19 stabilizes E-cadherin complexes at the cell membrane to maintain cell-cell adhesion which inhibits cell migration but provides growth and survival advantages for circulating tumor cells. These findings provide context-dependent roles of K19 during metastasis.

scholarly journals Keratin 19 maintains E-cadherin localization at the cell surface and stabilizes cell-cell adhesion of MCF7 cells

2021 ◽  
Vol 15 (1) ◽  
pp. 1-17
Author(s):  
Sarah Alsharif ◽  
Pooja Sharma ◽  
Karina Bursch ◽  
Rachel Milliken ◽  
Van Lam ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Mcf7 Cells ◽  
Keratin 19 ◽  
E Cadherin ◽  
Cell Cell

Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell–Cell Adhesion and Invasive Cell Migration in Human Breast Cancer

2014 ◽  
Vol 74 (11) ◽  
pp. 3054-3066 ◽  
Author(s):  
Emi Tokuda ◽  
Toshiki Itoh ◽  
Junya Hasegawa ◽  
Takeshi Ijuin ◽  
Yukiko Takeuchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Golgi Apparatus ◽  
Human Breast Cancer ◽  
Human Breast ◽  
Phosphatidylinositol 4 ◽  
Invasive Cell ◽  
Cell Cell

scholarly journals Tumorigenic epithelial clusters are less sensitive to moderate osmotic stresses due to low amounts of junctional E-cadherin

2020 ◽  
Author(s):  
Danahe Mohammed ◽  
Park Young Chan ◽  
Jeffrey J. Fredberg ◽  
David A. Weitz
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Epithelial Cells ◽  
Osmotic Stress ◽  
Metastatic Breast ◽  
Tumorigenic Cells ◽  
Breast Epithelial ◽  
The Impact ◽  
E Cadherin ◽  
Cell Cell

AbstractThe migration of tumorigenic epithelial cells is a critical step for metastatic breast cancer progression. Although the role of the extracellular matrix in breast cancer cell migration has been extensively described, the effect of osmotic stress on the migration of tumor breast epithelial cohorts remains unclear. Most of our understanding on the effect of osmotic stresses on cell migration comes from studies at the level of the single cell in isolation and does not take into account cell-cell interactions. Here, we study the impact of moderate osmotic stress on the migration of epithelial clusters composed of either non-tumorigenic or tumorigenic epithelial cells. We observe a decrease in migration distance and speed for non-tumorigenic epithelial cells but not for tumorigenic ones. To explain these differences, we investigate how osmotic stress impacts the mechanical properties of cell clusters and affects cell volumes. After application of osmotic stress renal epithelial cells become stiffer whereas non-tumorigenic and tumorigenic breast epithelial cells do not. In addition, tumorigenic cells are shown to be less sensitive to osmotic stress than non-tumorigenic cells, and this difference is associated with lower levels of E-cadherin expression. Using EGTA treatments, we confirm that the establishment of cell-cell adhesive interactions is a key component of the behavior of epithelial clusters in response to osmotic stress. This study provides evidence on the low sensitivity of tumorigenic epithelial clusters to moderate osmotic stress and highlights the importance of cadherin-based junctions in response to osmotic stress.

Isoform-specific function of calpains in cell adhesion disruption: studies in postlactational mammary gland and breast cancer

2016 ◽  
Vol 473 (18) ◽  
pp. 2893-2909 ◽  
Author(s):  
Lucía Rodríguez-Fernández ◽  
Iván Ferrer-Vicens ◽  
Concha García ◽  
Sara S. Oltra ◽  
Rosa Zaragozá ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Mammary Gland ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Proximity Ligation Assay ◽  
Specific Function ◽  
Adhesion Proteins ◽  
E Cadherin

Cleavage of adhesion proteins is the first step for physiological clearance of undesired cells during postlactational regression of the mammary gland, but also for cell migration in pathological states such as breast cancer. The intracellular Ca2+-dependent proteases, calpains (CAPNs), are known to cleave adhesion proteins. The isoform-specific function of CAPN1 and CAPN2 was explored and compared in two models of cell adhesion disruption: mice mammary gland during weaning-induced involution and breast cancer cell lines according to tumor subtype classification. In both models, E-cadherin, β-catenin, p-120, and talin-1 were cleaved as assessed by western blot analysis. Both CAPNs were able to cleave adhesion proteins from lactating mammary gland in vitro. Nevertheless, CAPN2 was the only isoform found to co-localize with E-cadherin in cell junctions at the peak of lactation. CAPN2/E-cadherin in vivo interaction, analyzed by proximity ligation assay, was dramatically increased during involution. Calpain inhibitor administration prevented the cytosolic accumulation of truncated E-cadherin cleaved by CAPN2. Conversely, in breast cancer cells, CAPN2 was restricted to the nuclear compartment. The isoform-specific expression of CAPNs and CAPN activity was dependent on the breast cancer subtype. However, CAPN1 and CAPN2 knockdown cells showed that cleavage of adhesion proteins and cell migration was mediated by CAPN1, independently of the breast cancer cell line used. Data presented here suggest that the subcellular distribution of CAPN1 and CAPN2 is a major issue in target-substrate recognition; therefore, it determines the isoform-specific role of CAPNs during disruption of cell adhesion in either a physiological or a pathological context.

scholarly journals Cellular crowd control: overriding endogenous cell coordination makes cell migration more susceptible to external programming

2021 ◽  
Author(s):  
Gawoon Shim ◽  
Danelle Devenport ◽  
Daniel J. Cohen
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Mouse Skin ◽  
Cellular Systems ◽  
Cell Junctions ◽  
External Control ◽  
Collective Behaviors ◽  
Primary Mouse ◽  
E Cadherin ◽  
Cell Cell

AbstractAs collective cell migration is essential in biological processes spanning development, healing, and cancer progression, methods to externally program cell migration are of great value. However, problems can arise if the external commands compete with strong, pre-existing collective behaviors in the tissue or system. We investigate this problem by applying a potent external migratory cue—electrical stimulation and electrotaxis—to primary mouse skin monolayers where we can tune cell-cell adhesion strength to modulate endogenous collectivity. Monolayers with high cell-cell adhesion showed strong natural coordination and resisted electrotactic control, with this conflict actively damaging the leading edge of the tissue. However, reducing pre-existing coordination in the tissue by specifically inhibiting E-cadherin-dependent cell-cell adhesion, either by disrupting the formation of cell-cell junctions with E-cadherin specific antibodies or rapidly dismantling E-cadherin junctions with calcium chelators, significantly improved controllability. Finally, we applied this paradigm of weakening existing coordination to improve control to demonstrate accelerated wound closure in vitro. These results are in keeping with those from diverse, non-cellular systems, and confirm that endogenous collectivity should be considered as a key, quantitative design variable when optimizing external control of collective migration.

scholarly journals Exogenous Expression of N-Cadherin in Breast Cancer Cells Induces Cell Migration, Invasion, and Metastasis

2000 ◽  
Vol 148 (4) ◽  
pp. 779-790 ◽  
Author(s):  
Rachel B. Hazan ◽  
Greg R. Phillips ◽  
Rui Fang Qiao ◽  
Larry Norton ◽  
Stuart A. Aaronson
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Matrix Protein ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Primary Tumors ◽  
Mcf 7 ◽  
E Cadherin

E- and N-cadherin are calcium-dependent cell adhesion molecules that mediate cell–cell adhesion and also modulate cell migration and tumor invasiveness. The loss of E-cadherin–mediated adhesion has been shown to play an important role in the transition of epithelial tumors from a benign to an invasive state. However, recent evidence indicates that another member of the cadherin family, N-cadherin, is expressed in highly invasive tumor cell lines that lacked E-cadherin expression. These findings have raised the possibility that N-cadherin contributes to the invasive phenotype. To determine whether N-cadherin promotes invasion and metastasis, we transfected a weakly metastatic and E-cadherin–expressing breast cancer cell line, MCF-7, with N-cadherin and analyzed the effects on cell migration, invasion, and metastasis. Transfected cells expressed both E- and N-cadherin and exhibited homotypic cell adhesion from both molecules. In vitro, N-cadherin–expressing cells migrated more efficiently, showed an increased invasion of Matrigel, and adhered more efficiently to monolayers of endothelial cells. All cells produced low levels of the matrix metalloproteinase MMP-9, which was dramatically upregulated by treatment with FGF-2 only in N-cadherin–expressing cells. Migration and invasion of Matrigel were also greatly enhanced by this treatment. When injected into the mammary fat pad of nude mice, N-cadherin–expressing cells, but not control MCF-7 cells, metastasized widely to the liver, pancreas, salivary gland, omentum, lung, lymph nodes, and lumbar spinal muscle. The expression of both E- and N-cadherin was maintained both in the primary tumors and metastatic lesions. These results demonstrate that N-cadherin promotes motility, invasion, and metastasis even in the presence of the normally suppressive E-cadherin. The increase in MMP-9 production by N-cadherin–expressing cells in response to a growth factor may endow them with a greater ability to penetrate matrix protein barriers, while the increase in their adherence to endothelium may improve their ability to enter and exit the vasculature, two properties that may be responsible for metastasis of N-cadherin–expressing cells.

scholarly journals WAVE2 Protein Complex Coupled to Membrane and Microtubules

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Kazuhide Takahashi
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Actin Assembly ◽  
Cell Migration And Invasion ◽  
Directional Cell Migration ◽  
E Cadherin ◽  
Cell Cell

E-cadherin is one of the key molecules in the formation of cell-cell adhesion and interacts intracellularly with a group of proteins collectively named catenins, through which the E-cadherin-catenin complex is anchored to actin-based cytoskeletal components. Although cell-cell adhesion is often disrupted in cancer cells by either genetic or epigenetic alterations in cell adhesion molecules, disruption of cell-cell adhesion alone seems to be insufficient for the induction of cancer cell migration and invasion. A small GTP-binding protein, Rac1, induces the specific cellular protrusions lamellipodia via WAVE2, a member of WASP/WAVE family of the actin cytoskeletal regulatory proteins. Biochemical and pharmacological investigations have revealed that WAVE2 interacts with many proteins that regulate microtubule growth, actin assembly, and membrane targeting of proteins, all of which are necessary for directional cell migration through lamellipodia formation. These findings might have important implications for the development of effective therapeutic agents against cancer cell migration and invasion.

scholarly journals Tumorigenic mesenchymal clusters are less sensitive to moderate osmotic stresses due to low amounts of junctional E-cadherin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danahe Mohammed ◽  
Chan Young Park ◽  
Jeffrey J. Fredberg ◽  
David A. Weitz
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Osmotic Stress ◽  
Cancer Progression ◽  
Metastatic Breast ◽  
Cell Clusters ◽  
Tumorigenic Cells ◽  
The Impact ◽  
E Cadherin ◽  
Cell Cell

AbstractThe migration of tumorigenic cells is a critical step for metastatic breast cancer progression. Although the role of the extracellular matrix in breast cancer cell migration has been extensively described, the effect of osmotic stress on the migration of tumor breast cohorts remains unclear. Most of our understanding on the effect of osmotic stresses on cell migration comes from studies at the level of the single cell in isolation and does not take cell–cell interactions into account. Here, we study the impact of moderate osmotic stress on the migration of cell clusters composed of either non-tumorigenic or tumorigenic cells. We observe a decrease in migration distance and speed for non-tumorigenic cells but not for tumorigenic ones. To explain these differences, we investigate how osmotic stress impacts the mechanical properties of cell clusters and affects their volumes. Our findings show that tumorigenic mesenchymal cells are less sensitive to osmotic stress than non-tumorigenic cells and suggest that this difference is associated with a lower expression of E-cadherin. Using EGTA treatments, we confirm that the establishment of cell–cell adhesive interactions is a key component of the behavior of cell clusters in response to osmotic stress. This study provides evidence on the low sensitivity of mesenchymal tumorigenic clusters to moderate osmotic stress and highlights the importance of cadherin-based junctions in the response to osmotic stress.

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