scholarly journals Molecular and cellular mechanisms controlling integrin-mediated cell adhesion and tumor progression in ovarian cancer metastasis: a review

2021 ◽  
Author(s):  
Dolly Dhaliwal ◽  
Trevor G. Shepherd
Keyword(s):  
Ovarian Cancer ◽  
Cell Adhesion ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Tumor Formation ◽  
Primary Tumor Site ◽  
Adhesion Properties ◽  
Mesenchymal Transition ◽  
Tumor Dissemination ◽  
Cell Cell

AbstractEpithelial ovarian cancer (EOC) is the most lethal gynecological malignancy in the developed world. EOC metastasis is unique since malignant cells detach directly from the primary tumor site into the abdominal fluid and form multicellular aggregates, called spheroids, that possess enhanced survival mechanisms while in suspension. As such, altered cell adhesion properties are paramount to EOC metastasis with cell detachment from the primary tumor, dissemination as spheroids, and reattachment to peritoneal surfaces for secondary tumor formation. The ability for EOC cells to establish and maintain cell–cell contacts in spheroids is critical for cell survival in suspension. Integrins are a family of cell adhesion receptors that play a crucial role in cell–cell and cell-extracellular matrix interactions. These glycoprotein receptors regulate diverse functions in tumor cells and are implicated in multiple steps of cancer progression. Altered integrin expression is detected in numerous carcinomas, where they play a role in cell migration, invasion, and anchorage-independent survival. Like that observed for other carcinomas, epithelial-mesenchymal transition (EMT) occurs during metastasis and integrins can function in this process as well. Herein, we provide a review of the evidence for integrin-mediated cell adhesion mechanisms impacting steps of EOC metastasis. Taken together, targeting integrin function may represent a potential therapeutic strategy to inhibit progression of advanced EOC.

Multi-Scale Modeling of Cancer Cell Migration and Adhesion During Epithelial-to-Mesenchymal Transition

2011 ◽  
Author(s):  
Rachel Zielinski ◽  
Cosmin Mihai ◽  
Samir Ghadiali
Keyword(s):  
Cell Migration ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Formation ◽  
Cell Stiffness ◽  
Migration And Invasion ◽  
Limited Information ◽  
Primary Tumor Site ◽  
Mesenchymal Transition ◽  
Secondary Tumor ◽  
Cell Cell

Cancer is a leading cause of death in the US, and tumor cell metastasis and secondary tumor formation are key factors in the malignancy and prognosis of the disease. The regulation of cell motility plays an important role in the migration and invasion of cancer cells into surrounding tissues. The primary modes of increased motility in cancerous tissues may include collective migration of a group of epithelial cells during tumor growth and single cell migration of mesenchymal cells after detachment from the primary tumor site [1]. In epithelial cancers, metastasizing cells lose their cell-cell adhesions, detach from the tumor mass, begin expressing mesenchymal markers, and become highly motile and invasive, a process known as epithelial-to-mesenchymal transition (EMT) (Fig. 1) [2]. Although the cellular and biochemical signaling mechanisms underlying EMT have been studied extensively, there is limited information about the biomechanical mechanisms of EMT. In particular, it is not known how changes in cell mechanics (cell stiffness, cell-cell adhesion strength, traction forces) influence the detachment, migration and invasion processes that occur during metastasis.

scholarly journals Claudins and Gastric Cancer: An Overview

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 290
Author(s):  
Itaru Hashimoto ◽  
Takashi Oshima
Keyword(s):  
Gastric Cancer ◽  
Cell Adhesion ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Treatment Strategies ◽  
The Cancer Genome Atlas ◽  
Therapeutic Drug ◽  
Mesenchymal Transition ◽  
New Treatment ◽  
Cell Cell

Despite recent improvements in diagnostic ability and treatment strategies, advanced gastric cancer (GC) has a high frequency of recurrence and metastasis, with poor prognosis. To improve the treatment results of GC, the search for new treatment targets from proteins related to epithelial–mesenchymal transition (EMT) and cell–cell adhesion is currently being conducted. EMT plays an important role in cancer metastasis and is initiated by the loss of cell–cell adhesion, such as tight junctions (TJs), adherens junctions, desmosomes, and gap junctions. Among these, claudins (CLDNs) are highly expressed in some cancers, including GC. Abnormal expression of CLDN1, CLDN2, CLDN3, CLDN4, CLDN6, CLDN7, CLDN10, CLDN11, CLDN14, CLDN17, CLDN18, and CLDN23 have been reported. Among these, CLDN18 is of particular interest. In The Cancer Genome Atlas, GC was classified into four new molecular subtypes, and CLDN18–ARHGAP fusion was observed in the genomically stable type. An anti-CLDN18.2 antibody drug was recently developed as a therapeutic drug for GC, and the results of clinical trials are highly predictable. Thus, CLDNs are highly expressed in GC as TJs and are expected targets for new antibody drugs. Herein, we review the literature on CLDNs, focusing on CLDN18 in GC.

scholarly journals Glycosyltransferase POMGNT1 deficiency affects N-cadherin-mediated cell-cell adhesion

2020 ◽  
Author(s):  
Sina Ibne Noor ◽  
Marcus Hoffmann ◽  
Natalie Rinis ◽  
Markus F. Bartels ◽  
Patrick Winterhalter ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Symptoms ◽  
Adhesion Properties ◽  
Knock Out ◽  
Mesenchymal Transition ◽  
Transcriptional Changes ◽  
Cell Cell

AbstractDefects in protein O-mannosylation lead to severe congenital muscular dystrophies known as α-dystroglycanopathy. A hallmark of these diseases is the loss of the O-mannose-bound matriglycan on α-dystroglycan, which leads to a reduction in cell adhesion to the extracellular matrix. Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, are mainly associated with muscle-eye-brain (MEB) disease. In addition to defects in cell-extracellular matrix adhesion, aberrant cell-cell adhesion has occasionally been observed in response to defects in POMGNT1. However, direct molecular mechanisms are largely unknown. We used POMGNT1 knock-out HEK293T cells and fibroblasts from a MEB patient to gain a deeper insight into the molecular changes in POMGNT1 deficiency. A combination of biochemical and molecular biological techniques with proteomics, glycoproteomics and glycomics revealed that a lack of POMGNT1 activity strengthens cell-cell adhesion. We demonstrate that the altered intrinsic adhesion properties are due to an increased abundance of N-cadherin (N-Cdh). In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions. We found that in POMGNT1 deficient cells ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable to the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype. Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general, and suggests a previously underestimated impact of changes in O-mannosylation on N-glycosylation.

scholarly journals Microgravity Induces Transient EMT in Human Keratinocytes by Early Down-Regulation of E-Cadherin and Cell-Adhesion Remodeling

2020 ◽  
Vol 11 (1) ◽  
pp. 110
Author(s):  
Giulia Ricci ◽  
Alessandra Cucina ◽  
Sara Proietti ◽  
Simona Dinicola ◽  
Francesca Ferranti ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Human Keratinocytes ◽  
Short Exposure ◽  
Migration And Invasion ◽  
Hacat Cells ◽  
Invasive Phenotype ◽  
Adhesion Properties ◽  
Mesenchymal Transition ◽  
Cell Matrix ◽  
E Cadherin

Changes in cell–matrix and cell-to-cell adhesion patterns are dramatically fostered by the microgravity exposure of living cells. The modification of adhesion properties could promote the emergence of a migrating and invasive phenotype. We previously demonstrated that short exposure to the simulated microgravity of human keratinocytes (HaCaT) promotes an early epithelial–mesenchymal transition (EMT). Herein, we developed this investigation to verify if the cells maintain the acquired invasive phenotype after an extended period of weightlessness exposure. We also evaluated cells’ capability in recovering epithelial characteristics when seeded again into a normal gravitational field after short microgravity exposure. We evaluated the ultra-structural junctional features of HaCaT cells by Transmission Electron Microscopy and the distribution pattern of vinculin and E-cadherin by confocal microscopy, observing a rearrangement in cell–cell and cell–matrix interactions. These results are mirrored by data provided by migration and invasion biological assay. Overall, our studies demonstrate that after extended periods of microgravity, HaCaT cells recover an epithelial phenotype by re-establishing E-cadherin-based junctions and cytoskeleton remodeling, both being instrumental in promoting a mesenchymal–epithelial transition (MET). Those findings suggest that cytoskeletal changes noticed during the first weightlessness period have a transitory character, given that they are later reversed and followed by adaptive modifications through which cells miss the acquired mesenchymal phenotype.

scholarly journals LncRNA SPOCD1-AS from ovarian cancer extracellular vesicles remodels mesothelial cells to promote peritoneal metastasis via interacting with G3BP1

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Conghui Wang ◽  
Jiaying Wang ◽  
Xiameng Shen ◽  
Mingyue Li ◽  
Yongfang Yue ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Extracellular Vesicles ◽  
Peritoneal Metastasis ◽  
Cancer Metastasis ◽  
Cancer Therapeutics ◽  
Mesothelial Cells ◽  
Ovarian Cancer Cells ◽  
Adhesion Assay ◽  
Mesenchymal Transition

Abstract Background Metastasis is the key cause of death in ovarian cancer patients. To figure out the biological nature of cancer metastasis is essential for developing effective targeted therapy. Here we investigate how long non-coding RNA (lncRNA) SPOCD1-AS from ovarian cancer extracellular vesicles (EVs) remodel mesothelial cells through a mesothelial-to-mesenchymal transition (MMT) manner and facilitate peritoneal metastasis. Methods EVs purified from ovarian cancer cells and ascites of patients were applied to mesothelial cells. The MMT process of mesothelial cells was assessed by morphology observation, western blot analysis, migration assay and adhesion assay. Altered lncRNAs of EV-treated mesothelial cells were screened by RNA sequencing and identified by qRT-PCR. SPOCD1-AS was overexpressed or silenced by overexpression lentivirus or shRNA, respectively. RNA pull-down and RNA immunoprecipitation assays were conducted to reveal the mechanism by which SPOCD1-AS remodeled mesothelial cells. Interfering peptides were synthesized and applied. Ovarian cancer orthotopic implantation mouse model was established in vivo. Results We found that ovarian cancer-secreted EVs could be taken into recipient mesothelial cells, induce the MMT phenotype and enhance cancer cell adhesion to mesothelial cells. Furthermore, SPOCD1-AS embedded in ovarian cancer-secreted EVs was transmitted to mesothelial cells to induce the MMT process and facilitate peritoneal colonization in vitro and in vivo. SPOCD1-AS induced the MMT process of mesothelial cells via interacting with G3BP1 protein. Additionally, G3BP1 interfering peptide based on the F380/F382 residues was able to block SPOCD1-AS/G3BP1 interaction, inhibit the MMT phenotype of mesothelial cells, and diminish peritoneal metastasis in vivo. Conclusions Our findings elucidate the mechanism associated with EVs and their cargos in ovarian cancer peritoneal metastasis and may provide a potential approach for metastatic ovarian cancer therapeutics.

Aquaporin-5 regulation of cell-cell adhesion proteins: an elusive "tail" story

2020 ◽  
Author(s):  
Frédéric H. Login ◽  
Johan Palmfeldt ◽  
Joleen Cheah ◽  
Soichiro Yamada ◽  
Lene N. Nejsum
Keyword(s):  
Cell Adhesion ◽  
Water Transport ◽  
Epithelial Mesenchymal Transition ◽  
Tail Domain ◽  
Aquaporin 5 ◽  
Mesenchymal Transition ◽  
Cancer Spread ◽  
Aqp5 Expression ◽  
Migration Capacity ◽  
Cell Cell

Aquaporins (AQPs) are water channels that facilitate transport of water across cellular membranes. AQPs are overexpressed in several cancers. Especially in breast cancer, AQP5 overexpression correlates with spread to lymph nodes and poor prognosis. Previously, we showed that AQP5 expression reduced cell-cell adhesion by reducing levels of adherens and tight junction proteins (e.g., ZO1, plakoglobin and β-catenin) at the actual junctions. Here, we show that when targeted to the plasma membrane, the AQP5 C-terminal tail domain regulated junctional proteins. Moreover, that AQP5 interacted with ZO1, plakoglobin, β-catenin and desmoglein-2, which were all reduced at junctions upon AQP5 overexpression. Thus, our data suggest that AQP5 mediates the effect on cell-cell adhesion via interactions with junctional protein independently of AQP5 mediated water transport. AQP5 overexpression in cancers may thus contribute to carcinogenesis and cancer spread by two independent mechanisms: reduced cell-cell adhesion, a characteristic of epithelial-mesenchymal transition, and increased cell migration capacity via water transport.

scholarly journals The Role of Immunoglobulin Superfamily Cell Adhesion Molecules in Cancer Metastasis

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Chee Wai Wong ◽  
Danielle E. Dye ◽  
Deirdre R. Coombe
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cancer Progression ◽  
Cell Adhesion Molecules ◽  
Cancer Metastasis ◽  
Clinical Problem ◽  
Metastatic Lesion ◽  
Immunoglobulin Superfamily ◽  
Metastatic Pathway ◽  
Cell Cell

Metastasis is a major clinical problem and results in a poor prognosis for most cancers. The metastatic pathway describes the process by which cancer cells give rise to a metastatic lesion in a new tissue or organ. It consists of interconnecting steps all of which must be successfully completed to result in a metastasis. Cell-cell adhesion is a key aspect of many of these steps. Adhesion molecules belonging to the immunoglobulin superfamily (Ig-SF) commonly play a central role in cell-cell adhesion, and a number of these molecules have been associated with cancer progression and a metastatic phenotype. Surprisingly, the contribution of Ig-SF members to metastasis has not received the attention afforded other cell adhesion molecules (CAMs) such as the integrins. Here we examine the steps in the metastatic pathway focusing on how the Ig-SF members, melanoma cell adhesion molecule (MCAM), L1CAM, neural CAM (NCAM), leukocyte CAM (ALCAM), intercellular CAM-1 (ICAM-1) and platelet endothelial CAM-1 (PECAM-1) could play a role. Although much remains to be understood, this review aims to raise the profile of Ig-SF members in metastasis formation and prompt further research that could lead to useful clinical outcomes.

Abstract A7: Targeting mutant p53 and cell-cell adhesion in ovarian cancer

2013 ◽  
Author(s):  
Marcin P. Iwanicki ◽  
Marian Novak ◽  
Ioannis K. Zervantonakis ◽  
Tan A. Ince ◽  
Ronny Drapkin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Adhesion ◽  
Mutant P53 ◽  
Cell Cell

scholarly journals The Impact of Spaceflight and Simulated Microgravity on Cell Adhesion

2020 ◽  
Vol 21 (9) ◽  
pp. 3031 ◽  
Author(s):  
Xiao Lin ◽  
Kewen Zhang ◽  
Daixu Wei ◽  
Ye Tian ◽  
Yongguang Gao ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Mammalian Cells ◽  
Simulated Microgravity ◽  
General Term ◽  
Cellular Adhesion ◽  
Immunoglobulin Superfamily ◽  
Adhesion Properties ◽  
Cellular Adhesion Molecule ◽  
The Impact ◽  
Cell Cell

Microgravity induces a number of significant physiological changes in the cardiovascular, nervous, immune systems, as well as the bone tissue of astronauts. Changes in cell adhesion properties are one aspect affected during long-term spaceflights in mammalian cells. Cellular adhesion behaviors can be divided into cell–cell and cell–matrix adhesion. These behaviors trigger cell–cell recognition, conjugation, migration, cytoskeletal rearrangement, and signal transduction. Cellular adhesion molecule (CAM) is a general term for macromolecules that mediate the contact and binding between cells or between cells and the extracellular matrix (ECM). In this review, we summarize the four major classes of adhesion molecules that regulate cell adhesion, including integrins, immunoglobulin superfamily (Ig-SF), cadherins, and selectin. Moreover, we discuss the effects of spaceflight and simulated microgravity on the adhesion of endothelial cells, immune cells, tumor cells, stem cells, osteoblasts, muscle cells, and other types of cells. Further studies on the effects of microgravity on cell adhesion and the corresponding physiological behaviors may help increase the safety and improve the health of astronauts in space.

scholarly journals Minireview: Steroid Receptor Coactivator-3: A Multifarious Coregulator in Mammary Gland Metastasis

Endocrinology ◽  
2011 ◽  
Vol 152 (1) ◽  
pp. 19-25 ◽  
Author(s):  
John P. Lydon ◽  
Bert W. O'Malley
Keyword(s):  
Mammary Gland ◽  
Growth Factor ◽  
Tumor Cell ◽  
Primary Tumor ◽  
Steroid Receptor ◽  
Tumor Formation ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Steroid Receptor Coactivator ◽  
Tumor Cell Motility

Abstract A member of the steroid receptor coactivator (SRC)/p160 family, SRC-3 acts as a coregulator for nuclear receptor (NR) and non-NR transcription factors. Such coregulator pleiotropy enables SRC-3 to influence a myriad of signaling networks that are essential for normal physiology and pathophysiology. Although SRC-3’s proliferative role in primary tumor formation in the mammary gland is well established, a role for this oncogenic coregulator in tumor cell motility and invasion has only recently been elucidated. In the nucleus, SRC-3 is required for the execution of the epithelial–mesenchymal transition, a programming step which endows an immotile cancer cell with motile and invasive characteristics. Nuclear SRC-3 is also essential for proteolytic breakdown of the extracellular matrix by matrix-metalloproteinases, a process which enables primary tumor cell invasion into the surrounding stroma. At the plasma membrane, however, a truncated isoform of SRC-3 (SRC-3Δ4) serves as a signaling adaptor for the epidermal growth factor→focal adhesion kinase→c-Src signal transduction pathway, a signaling cascade that is central to growth factor–induced cell migration and invasion. Together, these studies underscore a pivotal role for SRC-3 not only as a proto-oncogene but also as a prometastatic factor during the early steps in the invasion-metastasis cascade. Beyond furnishing critical mechanistic insights into SRC-3’s involvement in mammary tumor progression, these findings provide opportunities to develop new approaches for breast cancer diagnosis and intervention.

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