scholarly journals Extracellular Matrix-Mediated Breast Cancer Cells Morphological Alterations, Invasiveness, and Microvesicles/Exosomes Release

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2031
Author(s):  
Marco Franchi ◽  
Zoi Piperigkou ◽  
Konstantinos-Athanasios Karamanos ◽  
Leonardo Franchi ◽  
Valentina Masola
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Breast Cancer Cells ◽  
Morphological Changes ◽  
Metastatic Potential ◽  
Cancer Cell Invasion ◽  
Collagen Network ◽  
Morphological Alterations

Breast cancer is a leading disease in women. Several studies are focused to evaluate the critical role of extracellular matrix (ECM) in various biochemical and molecular aspects but also in terms of its effect on cancer cell morphology and therefore on cancer cell invasion and metastatic potential. ECM fibrillar components, such as collagen and fibronectin, affect cell behavior and properties of mammary cancer cells. The aim of this study was to investigate using the scanning electron microscopy (SEM) how the highly invasive MDA-MB-231 breast cancer cells, interplaying with ECM substrates during cell migration/invasion, modify their morphological characteristics and cytoplasmic processes in relation to their invasive potential. In particular we reproduced and analyzed how natural structural barriers to cancer cell invasion, such as the basement membrane (Matrigel) and fibrillar components of dermis (fibronectin as well as the different concentrations/array of type I collagen), could induce morphological changes in 3D cultures. Interestingly, we demonstrate that, even with different effects, all collagen concentrations/arrays lead to morphological alterations of breast cancer cells. Intriguingly, the elongated mesenchymal shaped cells were more prominent in 3D cultures with a dense and thick substrate (thick Matrigel, high concentrated collagen network, and densely packed collagen fibers), even though cells with different shape produced and released microvesicles and exosomes as well. It is therefore evident that the peri-tumoral collagen network may act not only as a barrier but also as a dynamic scaffold which stimulates the morphological changes of cancer cells, and modulates tumor development and metastatic potential in breast cancer.

scholarly journals The antihyperlipidemic drug Potassium Piperate impairs migration and tumorgenesis of breast cancer cells via upregulation of miR-31

2021 ◽  
Author(s):  
Junping Lu ◽  
Xiaoxia Tian ◽  
Mailisu Mailisu ◽  
Morigen Morigen ◽  
Lifei Fan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Combination Treatment ◽  
Breast Cancer Cells ◽  
Target Genes ◽  
Cancer Cell Invasion

Abstract Background Breast cancer is a leading malignant tumor which causes deaths among women, and metastasis is the primary cause for mortality in breast cancer. Due to the involvement of many regulatory molecules and signaling pathways, the occurrence and development process of metastasis needs to be further studied. MicroRNAs (miRNAs) are ubiquitously expressed small non-coding RNAs that have been shown to play an important role in the diagnosis and treatment of many diseases, as well as constituting an attractive candidate to control metastasis. In this study, we tried to uncover the mechanism of GBK in impairing breast cancer cell invasion and metastasis.Methods We treated cancer cells with GBK or not, found its target miRNA by analyzed miRNA transcriptional changes and the miRNA target genes by performed with the QT-PCR and Western Blot. The proliferation of breast cancer cells in vitro and in vivo under combination treatment with GBK and DDP was measured by CCK-8 kit and the nude mice tumor formation experiment.Results We found tumor suppressor miR-31 was a main target of GBK. GBK treatment affected the epigenetic modification at CpG sites by downregulating DNA methyltransferases, thus the methylation levels at CpG of lncRNA LOC554202 decreased significantly, and in turn upregulating of both miR-31 and its host gene LOC554202 in breast cancer cells. We also observed significant inhibition of miR-31 target genes under GBK stimulation, including RhoA, WAVE3 and SATB2, which all closely related to cancer cell invasion, migration and proliferation. Furthermore, we revealed that combination treatment with GBK and DDP had synergistic and dose reduction potential in inhibiting the proliferation of breast cancer cells in vitro and in vivo, especially in TNBC.Conclusion This study further analyzes the target and underlying mechanism of GBK in inhibiting breast cancer migration and invasion, and provides theoretical support for the development of GBK as an auxiliary drug for clinical treatment.

Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion

2009 ◽  
Vol 284 (1) ◽  
pp. 80-85 ◽  
Author(s):  
Severin Pinilla ◽  
Eckhard Alt ◽  
F.J. Abdul Khalek ◽  
Constantin Jotzu ◽  
Fabian Muehlberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Invasion ◽  
Cancer Cell Invasion ◽  
Breast Cancer Cell Invasion ◽  
Resident Stem Cells ◽  
Promote Breast Cancer

scholarly journals Curcumin Down-Regulates Visfatin Expression and Inhibits Breast Cancer Cell Invasion

Endocrinology ◽  
2012 ◽  
Vol 153 (2) ◽  
pp. 554-563 ◽  
Author(s):  
Su-Ryun Kim ◽  
Hyun-Joo Park ◽  
Yun-Hee Bae ◽  
Soon-Cheol Ahn ◽  
Hee-Jun Wee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Cell Invasion ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Cancer Cell Invasion ◽  
Human Breast

Obesity is frequently associated with breast cancer. Such associations are possibly mediated by adipokines. Visfatin, an adipokine, has recently been shown to be related to the development and progression of breast cancer. Therefore, the down-regulation of visfatin may be a novel strategy for breast cancer therapy. Curcumin has anticancer activities by modulating multiple signaling pathways and genes. The purpose of this study was to investigate whether visfatin gene expression is affected by curcumin in human breast cancer cells and to characterize the functional role of visfatin in breast cancer. We found that the mRNA and protein levels of visfatin were down-regulated by curcumin in MDA-MB-231, MDA-MB-468, and MCF-7 breast cancer cells, along with decreased activity of constitutive nuclear factor (NF)-κB. We confirmed the repressive effect of curcumin on visfatin transcription by performing a visfatin promoter-driven reporter assay and identified two putative NF-κB-binding sites on visfatin promoter that are important for this effect. EMSA and chromatin immunoprecipitation analysis indicated the binding of p65 to the visfatin promoter, which was effectively blocked by curcumin. Enforced expression of p65 protein increased visfatin promoter activity, whereas blocking NF-κB signaling suppressed visfatin gene expression. Visfatin could enhance the invasion of MDA-MB-231 cells and also attenuate curcumin-induced inhibition of cell invasion; on the other hand, visfatin knockdown by small interfering RNA led to the reduction of cell invasion. Our data demonstrate, for the first time, that curcumin down-regulates visfatin gene expression in human breast cancer cells by a mechanism that is, at least in part, NF-κB dependent and suggest that visfatin may contribute to breast cancer cell invasion and link obesity to breast cancer development and progression.

scholarly journals Axl Phosphorylates Elmo Scaffold Proteins To Promote Rac Activation and Cell Invasion

2014 ◽  
Vol 35 (1) ◽  
pp. 76-87 ◽  
Author(s):  
Afnan Abu-Thuraia ◽  
Rosemarie Gauthier ◽  
Rony Chidiac ◽  
Yoshinori Fukui ◽  
Robert A. Screaton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Invasion ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Metastatic Progression ◽  
Nucleotide Exchange

The receptor tyrosine kinase Axl contributes to cell migration and invasion. Expression of Axl correlates with metastatic progression in cancer patients, yet the specific signaling events promoting invasion downstream of Axl are poorly defined. Herein, we report Elmo scaffolds to be direct substrates and binding partners of Axl. Elmo proteins are established to interact with Dock family guanine nucleotide exchange factors to control Rac-mediated cytoskeletal dynamics. Proteomics and mutagenesis studies reveal that Axl phosphorylates Elmo1/2 on a conserved carboxyl-terminal tyrosine residue. Upon Gas6-dependent activation of Axl, endogenous Elmo2 becomes phosphorylated on Tyr-713 and enters into a physical complex with Axl in breast cancer cells. Interfering with Elmo2 expression prevented Gas6-induced Rac1 activation in breast cancer cells. Similarly to blocking of Axl, Elmo2 knockdown or pharmacological inhibition of Dock1 abolishes breast cancer cell invasion. Interestingly, Axl or Elmo2 knockdown diminishes breast cancer cell proliferation. Rescue of Elmo2 knockdown cells with the wild-type protein but not with Elmo2 harboring Tyr-713-Phe mutations restores cell invasion and cell proliferation. These results define a new mechanism by which Axl promotes cell proliferation and invasion and identifies inhibition of the Elmo-Dock pathway as a potential therapeutic target to stop Axl-induced metastases.

scholarly journals L-plastin Ser5 phosphorylation is modulated by the PI3K/SGK pathway and promotes breast cancer cell invasiveness

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Raquel A. C. Machado ◽  
Dunja Stojevski ◽  
Sébastien De Landtsheer ◽  
Philippe Lucarelli ◽  
Alexandre Baron ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Breast Cancer Cells ◽  
Pi3k Pathway ◽  
Erk Mapk ◽  
Cell Invasiveness ◽  
Cancer Cell Invasiveness

AbstractBackgroundMetastasis is the predominant cause for cancer morbidity and mortality accounting for approximatively 90% of cancer deaths. The actin-bundling protein L-plastin has been proposed as a metastatic marker and phosphorylation on its residue Ser5 is known to increase its actin-bundling activity. We recently showed that activation of the ERK/MAPK signalling pathway leads to L-plastin Ser5 phosphorylation and that the downstream kinases RSK1 and RSK2 are able to directly phosphorylate Ser5. Here we investigate the involvement of the PI3K pathway in L-plastin Ser5 phosphorylation and the functional effect of this phosphorylation event in breast cancer cells.MethodsTo unravel the signal transduction network upstream of L-plastin Ser5 phosphorylation, we performed computational modelling based on immunoblot analysis data, followed by experimental validation through inhibition/overexpression studies and in vitro kinase assays. To assess the functional impact of L-plastin expression/Ser5 phosphorylation in breast cancer cells, we either silenced L-plastin in cell lines initially expressing endogenous L-plastin or neoexpressed L-plastin wild type and phosphovariants in cell lines devoid of endogenous L-plastin. The established cell lines were used for cell biology experiments and confocal microscopy analysis.ResultsOur modelling approach revealed that, in addition to the ERK/MAPK pathway and depending on the cellular context, the PI3K pathway contributes to L-plastin Ser5 phosphorylation through its downstream kinase SGK3. The results of the transwell invasion/migration assays showed that shRNA-mediated knockdown of L-plastin in BT-20 or HCC38 cells significantly reduced cell invasion, whereas stable expression of the phosphomimetic L-plastin Ser5Glu variant led to increased migration and invasion of BT-549 and MDA-MB-231 cells. Finally, confocal image analysis combined with zymography experiments and gelatin degradation assays provided evidence that L-plastin Ser5 phosphorylation promotes L-plastin recruitment to invadopodia, MMP-9 activity and concomitant extracellular matrix degradation.ConclusionAltogether, our results demonstrate that L-plastin Ser5 phosphorylation increases breast cancer cell invasiveness. Being a downstream molecule of both ERK/MAPK and PI3K/SGK pathways, L-plastin is proposed here as a potential target for therapeutic approaches that are aimed at blocking dysregulated signalling outcome of both pathways and, thus, at impairing cancer cell invasion and metastasis formation.

scholarly journals Receptor-Type Protein Tyrosine Phosphatase Alpha (PTPα) mediates MMP14 localization and facilitates triple-negative breast cancer cell invasion.

2021 ◽  
pp. mbc.E20-01-0060
Author(s):  
Lisa R. Decotret ◽  
Brennan J. Wadsworth ◽  
Ling Vicky Li ◽  
Chinten J. Lim ◽  
Kevin L. Bennewith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Plasma Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Cell Invasion ◽  
Protein Tyrosine Phosphatase ◽  
Triple Negative ◽  
Tyrosine Phosphatase ◽  
Cancer Cell Invasion

The ability of cancer cells to invade into surrounding tissues requires degradation of the extracellular matrix (ECM). Invasive structures, such as invadopodia, form on the plasma membrane of cancer cells and secrete ECM-degrading proteases that play crucial roles in cancer cell invasion. We have previously shown that protein tyrosine phosphatase alpha (PTPα) regulates focal adhesion formation and migration of normal cells. Here we report a novel role for PTPα in promoting triple-negative breast cancer cell invasion in vitro and in vivo. We show that PTPα knockdown reduces ECM degradation and cellular invasion of MDA-MB-231 cells through Matrigel. PTPα is not a component of TKS5-positive structures resembling invadopodia; rather, PTPα localizes with endosomal structures positive for MMP14, caveolin-1, and early endosome antigen 1. Furthermore, PTPα regulates MMP14 localization to plasma membrane protrusions, suggesting a role for PTPα in intracellular trafficking of MMP14. Importantly, we show that orthotopic MDA-MB-231 tumours depleted of PTPα exhibit reduced invasion into the surrounding mammary fat pad. These findings suggest a novel role for PTPα in regulating the invasion of triple-negative breast cancer cells.

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