scholarly journals EphA2 cleavage by MT1-MMP triggers single cancer cell invasion via homotypic cell repulsion

2013 ◽  
Vol 201 (3) ◽  
pp. 467-484 ◽  
Author(s):  
Nami Sugiyama ◽  
Erika Gucciardo ◽  
Olga Tatti ◽  
Markku Varjosalo ◽  
Marko Hyytiäinen ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Cell Surface ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Cell Junction ◽  
Physical Interaction ◽  
Surface Complexes ◽  
Human Breast Carcinomas ◽  
Cell Cell

Changes in EphA2 signaling can affect cancer cell–cell communication and motility through effects on actomyosin contractility. However, the underlying cell–surface interactions and molecular mechanisms of how EphA2 mediates these effects have remained unclear. We demonstrate here that EphA2 and membrane-anchored membrane type-1 matrix metalloproteinase (MT1-MMP) were selectively up-regulated and coexpressed in invasive breast carcinoma cells, where, upon physical interaction in same cell–surface complexes, MT1-MMP cleaved EphA2 at its Fibronectin type-III domain 1. This cleavage, coupled with EphA2-dependent Src activation, triggered intracellular EphA2 translocation, as well as an increase in RhoA activity and cell junction disassembly, which suggests an overall repulsive effect between cells. Consistent with this, cleavage-prone EphA2-D359I mutant shifted breast carcinoma cell invasion from collective to rounded single-cell invasion within collagen and in vivo. Up-regulated MT1-MMP also codistributed with intracellular EphA2 in invasive cells within human breast carcinomas. These results reveal a new proteolytic regulatory mechanism of cell–cell signaling in cancer invasion.

scholarly journals CG7379/ING1 suppress cancer cell invasion by maintaining cell-cell junction integrity

2020 ◽  
Author(s):  
Alexandra D. Rusu ◽  
Zoe E. Cornhill ◽  
Brenda Canales Coutino ◽  
Marcos Castellanos Uribe ◽  
Anbarasu Lourdusamy ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cell Invasion ◽  
Control Cell ◽  
Septate Junction ◽  
Cell Junctions ◽  
Cell Junction ◽  
Cancer Cell Invasion ◽  
Cell Cell

AbstractApproximately 90% of cancer related deaths can be attributed to a tumour’s ability to spread. We have identified CG7379, the fly orthologue of human ING1, as a potent invasion suppressor. ING1 is a type II tumour suppressor with well-established roles in the transcriptional regulation of genes that control cell proliferation, response to DNA damage, oncogene-induced senescence and apoptosis. Recent work suggests a possible role for ING1 in cancer cell invasion and metastasis, but the molecular mechanism underlying this observation is lacking. Our results show that reduced expression of CG7379 promotes invasion in vivo in Drosophila, reduces the junctional localisation of several adherens and septate junction components, and severely disrupts cell-cell junction architecture. Similarly, ING1 knockdown significantly enhances invasion in vitro and disrupts E-cadherin distribution at cell-cell junctions. A transcriptome analysis reveals that loss of ING1 affects the expression of several junctional and cytoskeletal modulators, confirming ING1 as an invasion suppressor and a key regulator of cell-cell junction integrity.

scholarly journals CG7379 and ING1 suppress cancer cell invasion by maintaining cell–cell junction integrity

Open Biology ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 210077
Author(s):  
Alexandra D. Rusu ◽  
Zoe E. Cornhill ◽  
Brenda Canales Coutiño ◽  
Marcos Castellanos Uribe ◽  
Anbarasu Lourdusamy ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cell Invasion ◽  
Control Cell ◽  
Septate Junction ◽  
Cell Junctions ◽  
Cell Junction ◽  
Cancer Cell Invasion ◽  
Cell Cell

Approximately 90% of cancer-related deaths can be attributed to a tumour's ability to spread. We have identified CG7379, the fly orthologue of human ING1, as a potent invasion suppressor. ING1 is a type II tumour suppressor with well-established roles in the transcriptional regulation of genes that control cell proliferation, response to DNA damage, oncogene-induced senescence and apoptosis. Recent work suggests a possible role for ING1 in cancer cell invasion and metastasis, but the molecular mechanism underlying this observation is lacking. Our results show that reduced expression of CG7379 promotes invasion in vivo in Drosophila , reduces the junctional localization of several adherens and septate junction components, and severely disrupts cell–cell junction architecture. Similarly, ING1 knockdown significantly enhances invasion in vitro and disrupts E-cadherin distribution at cell–cell junctions. A transcriptome analysis reveals that loss of ING1 affects the expression of several junctional and cytoskeletal modulators, confirming ING1 as an invasion suppressor and a key regulator of cell–cell junction integrity.

scholarly journals MASKING ANTI-PHAGOCYTIC SIGNAL OF TUMOR BY PRO-PHAGOCYTIC SIGNAL-A KEY TO IMMUREMENT OF CANCER CELL

2016 ◽  
Vol 8 (9) ◽  
pp. 323
Author(s):  
Madheswaran Suresh ◽  
Malarvizhi Gurusamy ◽  
Natarajan Sudhakar
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Breast Carcinoma ◽  
Cell Surface ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Immune Surveillance ◽  
Phagocytic Cell ◽  
Surveillance Mechanism

<p>Immune surveillance is a mechanism where cells and tissues are watched constantly by ever alerted immune system. Most incipient cancer cells are recognized and eliminated by the immune surveillance mechanism, but still tumors have the ability to evade immune surveillance and immunological killing. One greater arm that tumor use to evade immune surveillance, is by expressing anti-phagocytic signal (CD47). Here we present a provocative hypothesis where cancer cells are removed alive by phagocytic cell (DC). That in turn will elicit effective and higher immunogenic condition. All this could be possible by addition pro-phagocytic signal (PtdSer) over cancer cell surface (Breast Cancer), that mask the presence of anti-phagocytic signal (CD47). In other words, adding eat me signal (PtdSer) over the breast cancer cell surface that mask the presence of don’t eat me signal or anti-phagocytic signal present in breast cancer cell surface. This could be possible by using bi-specific antibody, conjugated to PEG-modified liposomes, which carry (PtdSer) pro-phagocytic signal (or) eat me signal, which target both CD47 and EGFRVIII on breast carcinoma. The simultaneous masking of anti-phagocytic signal, and adding of pro–phagocytic signal over cancer cell, will enhance the phagocytic clearance of live tumor cell and elicit immunological killing.</p>

scholarly journals A Novel 3D Model for Visualization and Tracking of Fibroblast-Guided Directional Cancer Cell Migration

Biology ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 328
Author(s):  
Yihe Zhang ◽  
Bingjie Jiang ◽  
Meng Huee Lee
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Cell Mass ◽  
Physical Contact ◽  
Physical Interaction ◽  
Matrix Remodeling ◽  
Cancer Cell Migration ◽  
Cell Type

Stromal fibroblasts surrounding cancer cells are a major and important constituent of the tumor microenvironment not least because they contain cancer-associated fibroblasts, a unique fibroblastic cell type that promotes tumorigenicity through extracellular matrix remodeling and secretion of soluble factors that stimulate cell differentiation and invasion. Despite much progress made in understanding the molecular mechanisms that underpin fibroblast–tumor cross-talk, relatively little is known about the way the two cell types interact from a physical contact perspective. In this study, we report a novel three-dimensional dumbbell model that would allow the physical interaction between the fibroblasts and cancer cells to be visualized and monitored by microscopy. To achieve the effect, the fibroblasts and cancer cells in 50% Matrigel suspension were seeded as independent droplets in separation from each other. To allow for cell migration and interaction, a narrow passage of Matrigel causeway was constructed in between the droplets, effectively molding the gel into the shape of a dumbbell. Under time-lapse microscopy, we were able to visualize and image the entire process of fibroblast-guided cancer cell migration event, from initial vessel-like structure formation by the fibroblasts to their subsequent invasion across the causeway, attracting and trapping the cancer cells in the process. Upon prolonged culture, the entire population of fibroblasts eventually infiltrated across the passage and condensed into a spheroid-like cell mass, encapsulating the bulk of the cancer cell population within. Suitable for almost every cell type, our model has the potential for a wider application as it can be adapted for use in drug screening and the study of cellular factors involved in cell–cell attraction.

Intraoperative radiotherapy impairs breast cancer cell motility induced by surgical wound fluid

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10611-10611 ◽  
Author(s):  
S. Massarut ◽  
G. Baldassarre ◽  
B. Belletti ◽  
A. Colombatti ◽  
S. D'Andrea ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Breast Carcinoma ◽  
Cell Motility ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Intraoperative Radiotherapy ◽  
Breast Conserving Surgery ◽  
Surgical Wound ◽  
Wound Fluid

10611 Background: Most recurrences after breast conserving surgery for cancer occur in the tissues around the original tumour. Wound-fluid has been shown to induce proliferation of breast carcinoma cells. We investigated whether intraoperative radiotherapy (IORT) using the targeted intraoperative radiotherapy (Targit) technique changes the effect of surgical wound fluid on the behaviour of breast cancer cells. Methods: Preoperative peripheral blood serums (A) and wound fluid (B) (first 24 hours’s drainage) from 30 unselected patients undergoing breast conserving surgery with (14) or without (16) IORT using the Targit technique was collected, processed and stored at −80°C. The breast carcinoma cell lines (MDA-MB231, MDA-MB-45 and SKBR-3) were used to evaluate the activity of A and B on cell proliferation (MTT-FACS analysis) and motility (chemotaxis) and invasion (Matrigel). Results: Wound fluid stimulated cell proliferation, cell motility and cell invasion significantly more than the preoperative serum from the same patient. Targit did not influence the effect of wound fluid on cell proliferation. However, Targit abrogated the effect wound fluid on cell motility and cell invasion. Conclusions: This work demonstrates that wound fluid after surgery for breast cancer stimulates cancer cell growth and motility. Targit appears to significantly abrogate the effect on cancer cell migration and invasion. This outcome may confer more benefits than could be expected from the tumoricidal activity of radiotherapy, and may stimulate the development of novel peri-operative treatments directed at compensating the possible harmful effects of surgery. No significant financial relationships to disclose.

Identification of CD146 as a component of the endothelial junction involved in the control of cell-cell cohesion

Blood ◽  
2001 ◽  
Vol 98 (13) ◽  
pp. 3677-3684 ◽  
Author(s):  
Nathalie Bardin ◽  
Francine Anfosso ◽  
Jean-Marc Massé ◽  
Elisabeth Cramer ◽  
Florence Sabatier ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Umbilical Vein ◽  
Cell Surface Expression ◽  
Cell Junction ◽  
Immunoglobulin Superfamily ◽  
Cell Surface Molecule ◽  
Apical Side ◽  
Endothelial Junction ◽  
Cell Cell

Abstract CD146 is a cell-surface molecule belonging to the immunoglobulin superfamily and expressed in all types of human endothelial cells. Confocal and electron microscopic analysis of confluent human umbilical vein endothelial cells (HUVECs) were used to demonstrate that CD146 is a component of the endothelial junction. Double immunolabeling with vascular endothelial cadherin showed that CD146 is localized outside the adherens junction. Moreover, CD146 expression is not restricted to the junction, since part of the labeling was detectable at the apical side of the HUVECs. Interestingly, cell-surface expression of CD146 increased when HUVECs reached confluence. In addition, the paracellular permeability of CD146-transfected fibroblast cells was decreased compared with that of control cells. Finally, CD146 colocalized with actin, was partly resistant to Triton X-100 extraction, and had its expression altered by actin-disrupting agents, indicating that CD146 is associated with the actin cytoskeleton. These results show the regulated expression of CD146 at areas of cell-cell junction and strongly suggest involvement of CD146 as a mediator of cell-cell interaction.

scholarly journals Molecular mechanisms of cancer cell-cell interactions

2012 ◽  
Vol 6 (4) ◽  
pp. 344-345 ◽  
Author(s):  
Susann M. Brady-Kalnay
Keyword(s):  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Cell Interactions ◽  
Cell Cell

scholarly journals Calpain-2 regulates hypoxia/HIF-induced amoeboid reprogramming and metastasis

2020 ◽  
Author(s):  
Veronika te Boekhorst ◽  
Liying Jiang ◽  
Marius Mählen ◽  
Maaike Meerlo ◽  
Gina Dunkel ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Adaptor Protein ◽  
Pharmacological Intervention ◽  
Amoeboid Movement ◽  
Cancer Cell Invasion ◽  
Epithelial Cancers ◽  
Beta1 Integrin ◽  
Calpain 2

SummaryHypoxia, through hypoxia inducible factor (HIF), drives cancer cell invasion and metastatic progression in various cancer types, leading to poor prognosis. In epithelial cancer, hypoxia further induces the transition to amoeboid cancer cell dissemination, yet the molecular mechanisms, relevance for metastasis, and effective interventions to combat hypoxia-induced amoeboid reprogramming remain unclear. Here, we identify calpain-2 as key regulator and anti-metastasis target of hypoxia-induced transition from collective to amoeboid dissemination of breast and head and neck (HN) carcinoma cells. Hypoxia-induced amoeboid dissemination occurred through low ECM-adhesive, bleb-based amoeboid movement, which effectively invaded into 3D collagen with low-oxidative and -glycolytic energy metabolism, revealing an microenvironmentally-induced, energy-conserving dissemination route in epithelial cancers. Hypoxia-induced calpain-2 mediated amoeboid conversion by de-activating beta1 integrins, through enzymatic cleavage of the focal adhesion adaptor protein talin-1. Consequently, targeted downregulation of calpain-2 or pharmacological intervention restored talin-1 integrity, beta1 integrin engagement and reverted blebbing-amoeboid to elongated phenotypes under hypoxia. Calpain-2 activity was required for hypoxia-induced blebbing-amoeboid conversion in the orthotopic mouse dermis, and upregulated in invasive HN tumor xenografts in vivo, and attenuation of calpain activity prevented hypoxia-induced metastasis to the lungs. This identifies the calpain-2/talin-1/beta1 integrin axis as mechanosignaling program and promising intervention target of plasticity of cancer cell invasion and metastasis formation in epithelial cancers under hypoxia.

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