scholarly journals ECM cross-linking regulates invadopodia dynamics

2017 ◽  
Author(s):  
Kamyar Esmaeili ◽  
Aviv Bergman ◽  
Bojana Gligorijevic
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Time Lapse ◽  
Invasive Cancer ◽  
Cross Linking ◽  
Β1 Integrin ◽  
Cell Behaviors ◽  
Lysine Residues ◽  
Ecm Degradation ◽  
And Function

AbstractInvadopodiInvadopodia are membrane protrusions dynamically assembled by invasive cancer cells in contact with extracellular matrix (ECM). Invadopodia are enriched for the structural proteins actin and cortactin, as well as metalloproteases such as MT1-MMP, whose function is to degrade the surrounding ECM. During metastasis, invadopodia are necessary for cancer cell intravasation and extravasation. While signaling pathways involved in the assembly and function of invadopodia are well studied, few studies address invadopodia dynamics and how the cell-ECM interactions contribute to cell invasion. Using iterative analysis based on time-lapse microscopy and mathematical modeling of invasive cancer cells, we found that cells oscillate between invadopodia presence and cell stasis, termed Invadopodia state and invadopodia absence during cell translocation, termed Migration state. Our data suggests that β1-integrin-ECM binding and ECM cross-linking control the duration of each of the two states. By changing the concentration of cross-linkers in 2D and 3D cultures, we generate ECM where 0-0.92 of total lysine residues are cross-linked. Using ECM with a range of cross-linking degrees we demonstrate that the dynamics of invadopodia-related functions have a biphasic relationship to ECM cross-linking. At intermediate levels of ECM cross-linking (0.39), cells exhibit rapid invadopodia protrusion-retraction cycles and rapid calcium spikes, which lead to more frequent MT1-MMP delivery, causing maximal invadopodia-mediated ECM degradation. In contrast, both extremely high or low levels of cross-linking lead to slower invadopodia-related dynamics and lower ECM degradation. Additionally, β1-integrin inhibition modifies dynamics of invadopodia-related functions, as well as the length of time cells spend in either of the states. Collectively, these data suggest that β1-integrin-ECM binding non-linearly translates small physical differences in extracellular environment to differences in the dynamics of cancer cell behaviors. Understanding conditions under which invadopodia can be reduced by subtle environment-targeting treatments may lead to combination therapies for preventing metastatic spread.

scholarly journals Probing the mechanisms of extracellular vesicle biogenesis and function in cancer

2018 ◽  
Vol 46 (5) ◽  
pp. 1137-1146 ◽  
Author(s):  
Arash Latifkar ◽  
Richard A. Cerione ◽  
Marc A. Antonyak
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Extracellular Vesicle ◽  
Rna Transcripts ◽  
Main Class ◽  
Vesicle Biogenesis ◽  
And Migration ◽  
And Function ◽  
Cell Phenotypes

Tumor cells interact with each other, and their surroundings, using a variety of mechanisms to promote virtually all aspects of cancer progression. One such form of intercellular communication that has been attracting considerable attention from the cancer community and the pharmaceutical industry in recent years involves the ability of cancer cells to generate multiple distinct types of non-classical secretory vesicles, generally referred to as extracellular vesicles (EVs). Microvesicles (MVs) represent one of the major classes of EVs and are formed as a result of the outward budding and fission of the plasma membrane. The other main class of EVs is exosomes, which are generated when multivesicular bodies fuse with the cell surface and release their contents into the extracellular space. Both MVs and exosomes have been shown to contain bioactive cargo, including proteins, metabolites, RNA transcripts, microRNAs, and DNA that can be transferred to other cancer cells and stimulate their growth, survival, and migration. However, cancer cell-derived EVs also play important roles in helping re-shape the tumor microenvironment to support tumor expansion and invasive activity, dampen immune responses, as well as enter the circulation to help promote metastatic spread. Here, we provide an overview of what is currently known regarding how the different classes of EVs are generated and contribute to various cancer cell phenotypes. Moreover, we highlight how some of the unique properties of EVs are being used for the development of novel diagnostic and clinical applications.

scholarly journals Cdc42 promotes transendothelial migration of cancer cells through β1 integrin

2012 ◽  
Vol 199 (4) ◽  
pp. 653-668 ◽  
Author(s):  
Nicolas Reymond ◽  
Jae Hong Im ◽  
Ritu Garg ◽  
Francisco M. Vega ◽  
Barbara Borda d’Agua ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Serum Response Factor ◽  
Lung Metastases ◽  
Transendothelial Migration ◽  
Transcriptional Level ◽  
Β1 Integrin ◽  
Integrin Expression

Cancer cells interact with endothelial cells during the process of metastatic spreading. Here, we use a small interfering RNA screen targeting Rho GTPases in cancer cells to identify Cdc42 as a critical regulator of cancer cell–endothelial cell interactions and transendothelial migration. We find that Cdc42 regulates β1 integrin expression at the transcriptional level via the transcription factor serum response factor (SRF). β1 integrin is the main target for Cdc42-mediating interaction of cancer cells with endothelial cells and the underlying extracellular matrix, as exogenous β1 integrin expression was sufficient to rescue the Cdc42-silencing phenotype. We show that Cdc42 was required in vivo for cancer cell spreading and protrusion extension along blood vessels and retention in the lungs. Interestingly, transient Cdc42 depletion was sufficient to decrease experimental lung metastases, which suggests that its role in endothelial attachment is important for metastasis. By identifying β1 integrin as a transcriptional target of Cdc42, our results provide new insight into Cdc42 function.

scholarly journals miR-31 Is a Broad Regulator of β1-Integrin Expression and Function in Cancer Cells

2011 ◽  
Vol 9 (11) ◽  
pp. 1500-1508 ◽  
Author(s):  
Katarzyna Augoff ◽  
Mitali Das ◽  
Katarzyna Bialkowska ◽  
Brian McCue ◽  
Edward F. Plow ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Β1 Integrin ◽  
Integrin Expression ◽  
And Function

scholarly journals circCOL1A1 Promotes the Progression of Gastric Cancer Cells through Sponging miR-145 to Enhance RABL3 Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Yue Ma ◽  
Yanyi Ren ◽  
Huitao Wen ◽  
Chengcheng Cui
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines ◽  
Microrna Sponge ◽  
And Function

Circular RNA has been reported to be a new noncoding RNA which plays important roles in tumor progression. One of the most common functions of circular RNA is to regulate microRNA expression by acting as a microRNA sponge. However, the circular RNA expression profile and function remain mostly unclear in gastric cancer. In the study, we explored the expression and function of circCOL1A1 (hsa_circ_0044556) in gastric cancer. We performed RT-PCR with divergent primers, mRNA stability assay, and RNase R digestion assay to characterize circCOL1A1 in gastric cancer cell lines. qRT-PCR was applied to detect the level of circCOL1A1 in both gastric cancer cell lines and tissues. Gain- and loss-of-function studies were carried out to detect the influence of circCOL1A1 on gastric cancer cells by performing CCK8, migration, and invasion assays. The regulation of the downstream genes was identified by qRT-PCR, western blot assay, dual luciferase assay, and RNA pull-down assay. The results showed that circCOL1A1 was highly expressed in both gastric cancer cells and tissues. Silence of circCOL1A1 inhibited the proliferation, migration, and invasion of gastric cancer cells. circCOL1A1 regulated the expression of miR-145 by acting as a microRNA sponge, and the influence of circCOL1A1 could be abrogated by miR-145 mimics. Our research shows that miR-145 plays its functions through targeting and regulating RABL3. Inhibition of circCOL1A1/miR-145/RABL3 could effectively suppress gastric cancer cell proliferation, migration, and invasion. circCOL1A1 also promote the transformation of M1 into M2 macrophage. Our study identified circCOL1A1 as a novel oncogenic circRNA and will provide more information for gastric cancer therapy.

scholarly journals Control of dynamic cell behaviors during angiogenesis and anastomosis by Rasip 1

2020 ◽  
Author(s):  
Minkyoung Lee ◽  
Charles Betz ◽  
Ilkka Paatero ◽  
Niels Schellinx ◽  
Jianmin Yin ◽  
...  
Keyword(s):  
Time Lapse ◽  
Tube Formation ◽  
Interacting Protein ◽  
Cell Behaviors ◽  
Sprouting Angiogenesis ◽  
Phenotype Analysis ◽  
Membrane Compartment ◽  
Dynamic Cell ◽  
Cellular Behaviors ◽  
And Function

AbstractOrgan morphogenesis is driven by a wealth of tightly orchestrated cellular behaviors, which ensure proper organ assembly and function. Many of these cell activities involve cell-cell interactions and remodeling of the F-actin cytoskeleton. Here, we analyze the requirement for Rasip1 (Ras-interacting protein 1), an endothelial-specific regulator of junctional dynamics, during blood vessel formation. Phenotype analysis of rasip1 mutants in zebrafish embryos reveal distinct requirements for Rasip1 during sprouting angiogenesis, vascular anastomosis and lumen formation. During angiogenic sprouting, Rasip1 is required for efficient cell pairing, which is essential for multicellular tube formation. High-resolution time-lapse analyses show that these cell pairing defects are caused by a destabilization of tricellular junctions suggesting that tri-cellular junctions may serve as a counterfort to tether sprouting endothelial cells during morphogenetic cell rearrangements. During anastomosis, Rasip1 is required to establish a stable apical membrane compartment; rasip1 mutants display ectopic, reticulated junctions and the apical compartment is frequently collapsed. Loss of Ccm1 and Heg1 function leads to junctional defects similar to those seen in rasip1 mutants. Analysis of radil-b single and rasip1/radil-b double mutants reveal distinct and overlapping functions of both proteins. While Rasip1 and Radil-b have similar functions during angiogenic sprouting, the junction formation during anastomosis may primarily depend on Rasip1.

Cancer Cell Growth in the Near Infrared Region by Using Silica Coated Gold Nanorods

NANO ◽  
2020 ◽  
Vol 15 (01) ◽  
pp. 2050001 ◽  
Author(s):  
Tuntun Wang ◽  
Kwi Seok Yeom ◽  
Sitansu Sekhar Nanda ◽  
Seong Soo A. An ◽  
Dong Kee Yi
Keyword(s):  
Protein Folding ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gold Nanorods ◽  
Near Infrared ◽  
Infrared Region ◽  
Cancer Cell Growth ◽  
Growth And Survival ◽  
Cell Behaviors

Gold nanorods (AuNRs) have been considered as suitable materials for diverse biomedical applications in controlling cell behaviors. The nanoisland system with well-dispersed silica coated Au nanorods (Si-AuNRs) was used to demonstrate the enhanced cell growth of normal and cancer cells (MDA-MB-231 mammalian breast cancer cells) from the induced expressions of the heat shock proteins (HSPs). The over-expressions of HSP could help in protein folding in cell proliferations and growths of both the normal and cancer cells. In the current study, interesting mechanisms of cancer cell growth with Si-AuNRs than the conventional systems, such as incubator, would be presented. We believe that the growth of cancer cells in near infrared (NIR) region using Si-AuNRs induced the activities of HSPs, which could help the protein folding in cell growth and survival in comparison to the cells grown in the incubator only. The cell growth enhancing technology could be expanded in diverse applications in cell culture systems.

Effect of anti-β1 integrin antibody on lung seeding of osteosarcoma cells in live mice visualized by single-cell in vivo imaging.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10072-10072
Author(s):  
Hiroaki Kimura ◽  
Yasunori Tome ◽  
Masashi Momiyama ◽  
Katsuhiro Hayashi ◽  
Michael Bouvet ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
In Vivo Imaging ◽  
Fluorescent Protein ◽  
Β1 Integrin ◽  
Cell Seeding ◽  
Osteosarcoma Cells ◽  
Single Cancer

10072 Background: Integrins play a role in tumor growth and metastasis (Int. J. Cancer 129, 2905-2915, 2011). However, the effect of integrin inhibition has not been visualized on single cancer cells in vivo. In this study, we used a powerful subcellular in vivo imaging model to demonstrate how an anti-integrin antibody affects seeding and growth of osteosarcoma cells on the lung. Methods: The 143B human osteosarcoma cell line expressing red fluorescent protein (RFP) in the cytoplasm and green fluorescent protein (GFP) in the nucleus was established. Using the double-labeled osteosarcoma cells, single cancer-cell seeding in the lung after i.v. injection of osteosarcoma cells was imaged in live mice. Results: The anti-b1 integrin monoclonal antibody, AIIB2, greatly inhibited the seeding of cancer cells on the lung while a control antibody had no effect. To image the efficacy of the anti-integrin antibody on spontaneous metastasis, mice with orthotopically-growing 143B-RFP cells in the tibia were also treated with AIIB2 or control anti-rat IgG1 antibody. After 3 weeks treatment, mice were sacrificed and primary tumors and lung metastases were evaluated with fluorescence imaging. AIIB2 significantly inhibited spontaneous lung metastasis but not primary tumor growth. In a separate experiment, the anti-β1 integrin antibody increased survival in the orthothopic osteosarcoma model. Conclusions: The efficacy of the anti-β1 integrin antibody against metastasis may be due to inhibition of lung seeding of the cancer cells. The increased survival of mice with orthotopically-growing 143B-RFP treated with AIIB2 may be due to inhibition of metastasis, which in turn may be inhibited by effect of the anti-β1 integrin on cancer-cell seeding in the lung.

Measuring systematic changes in invasive cancer cell shape using Zernike moments

2016 ◽  
Vol 8 (11) ◽  
pp. 1183-1193 ◽  
Author(s):  
Elaheh Alizadeh ◽  
Samanthe Merrick Lyons ◽  
Jordan Marie Castle ◽  
Ashok Prasad
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Shape ◽  
Zernike Moments ◽  
Invasive Cancer ◽  
Two Dimensional ◽  
Dimensional Cell ◽  
Invasive Cancer Cell

Cancer cells show similar changes in two dimensional cell shape analyzed using Zernike moments.

scholarly journals CD44 cross-linking increases malignancy of breast cancer via upregulation of p-Moesin

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Song Hu ◽  
Xiaoxing Shi ◽  
Yiwen Liu ◽  
Yiqing He ◽  
Yan Du ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Tumor Metastasis ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Cross Linking ◽  
Cell Metastasis ◽  
Cancer Tissues

Abstract Background CD44 is highly expressed in most cancer cells and its cross-linking pattern is closely related to tumor migration and invasion. However, the underlying molecular mechanism regarding CD44 cross-linking during cancer cell metastasis is poorly understood. Therefore, the purpose of this study was to explore whether disruption of CD44 cross-linking in breast cancer cells could prevent the cells migration and invasion and determine the effects of CD44 cross-linking on the malignancy of the cancer cells. Methods The expression of CD44, CD44 cross-linking and Moesin phosphorylation in breast cancer cells was assessed by Western Blot assays. Effects of CD44 cross-linking on tumor metastasis were evaluated by Transwell assay. The effects of CD44 cross-linking disruption on cell viability were assessed using CCK-8 assays. The expression of p-Moesin between normal and breast cancer tissues was examined by immunohistochemical staining. Results High expression of CD44 cross-linking was found in invasive breast cancer cells (BT-549 and MDA-MB-231), which is associated with the malignancy of breast cancer. The expressions of ERM complex in a panel of breast cancer cell lines indicate that Moesin and its phosphorylation may play a significant role in cell metastasis. Moesin phosphorylation was inhibited by CD44 de-crosslinking in breast cancer cells and Moesin shRNA knockdown attenuated the promotion of CD44 cross-linking on cell migration and invasion. Finally, immunohistochemistry results demonstrated that p-Moesin was overexpressed in primary and metastatic cancers. Conclusions Our study suggested that CD44 cross-linking could elevate p-Moesin expression and further affect migration and invasion of breast cancer cells. These results also indicate that p-Moesin may be useful in future targeted cancer therapy.

scholarly journals Mammalian SIRT6 Represses Invasive Cancer Cell Phenotypes through ATP Citrate Lyase (ACLY)-Dependent Histone Acetylation

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1460
Author(s):  
Wei Zheng ◽  
Luisa Tasselli ◽  
Tie-mei Li ◽  
Katrin F. Chua
Keyword(s):  
Gene Expression ◽  
Histone Acetylation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Invasive Cancer ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase ◽  
Cell Phenotypes ◽  
Invasive Cancer Cell

The modulation of dynamic histone acetylation states is key for organizing chromatin structure and modulating gene expression and is regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes. The mammalian SIRT6 protein, a member of the Class III HDAC Sirtuin family of NAD+-dependent enzymes, plays pivotal roles in aging, metabolism, and cancer biology. Through its site-specific histone deacetylation activity, SIRT6 promotes chromatin silencing and transcriptional regulation of aging-associated, metabolic, and tumor suppressive gene expression programs. ATP citrate lyase (ACLY) is a nucleo-cytoplasmic enzyme that produces acetyl coenzyme A (acetyl-CoA), which is the required acetyl donor for lysine acetylation by HATs. In addition to playing a central role in generating cytosolic acetyl-CoA for de novo lipogenesis, a growing body of work indicates that ACLY also functions in the nucleus where it contributes to the nutrient-sensitive regulation of nuclear acetyl-CoA availability for histone acetylation in cancer cells. In this study, we have identified a novel function of SIRT6 in controlling nuclear levels of ACLY and ACLY-dependent tumor suppressive gene regulation. The inactivation of SIRT6 in cancer cells leads to the accumulation of nuclear ACLY protein and increases nuclear acetyl-CoA pools, which in turn drive locus-specific histone acetylation and the expression of cancer cell adhesion and migration genes that promote tumor invasiveness. Our findings uncover a novel mechanism of SIRT6 in suppressing invasive cancer cell phenotypes and identify acetyl-CoA responsive cell migration and adhesion genes as downstream targets of SIRT6.

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