scholarly journals ΕGFR/ERβ-Mediated Cell Morphology and Invasion Capacity Are Associated with Matrix Culture Substrates in Breast Cancer

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2256
Author(s):  
Konstantina Kyriakopoulou ◽  
Eirini Riti ◽  
Zoi Piperigkou ◽  
Konstantina Koutroumanou Sarri ◽  
Heba Bassiony ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Morphology ◽  
Breast Cancer Cells ◽  
Type I Collagen ◽  
Morphological Characteristics ◽  
Migration And Invasion ◽  
Type I ◽  
Egfr Inhibition ◽  
The Impact

Breast cancer accounts for almost one in four cancer diagnoses in women. Studies in breast cancer patients have identified several molecular markers, indicators of aggressiveness, which help toward more individual therapeutic approaches. In triple-negative breast cancer (TNBC), epidermal growth factor receptor (EGFR) overexpression is associated with increased metastatic potential and worst survival rates. Specifically, abnormal EGFR activation leads to altered matrix metalloproteinases’ (MMPs) expression and, hence, extracellular matrix (ECM) degradation, resulting in induced migration and invasion. The use of matrix substrates for cell culture gives the opportunity to mimic the natural growth conditions of the cells and their microenvironment, as well as cell–cell and cell–matrix interactions. The aim of this study was to evaluate the impact of EGFR inhibition, estrogen receptor beta (ERβ) and different matrix substrates [type I collagen and fibronectin (FN)] on the functional properties, expression of MMPs and cell morphology of ERβ-positive TNBC cells and shERβ ones. Our results highlight EGFR as a crucial regulator of the expression and activity levels of MMPs, while ERβ emerges as a mediator of MMP7 and MT1-MMP expression. In addition, the EGFR/ERβ axis impacts the adhesion and invasion potential of breast cancer cells on collagen type I. Images obtained by scanning electron microscope (SEM) from cultures on the different matrix substrates revealed novel observations regarding various structures of breast cancer cells (filopodia, extravesicles, tunneling nanotubes, etc.). Moreover, the significant contribution of EGFR and ERβ in the morphological characteristics of these cells is also demonstrated, hence highlighting the possibility of dual pharmacological targeting.

scholarly journals Migration of breast cancer cells into reconstituted type I collagen gels assessed via a combination of frozen sectioning and azan staining

2014 ◽  
Vol 8 (4) ◽  
pp. 212-216 ◽  
Author(s):  
Kyohei Fukuda ◽  
Yo Kamoshida ◽  
Taisuke Kurokawa ◽  
Mioto Yoshida ◽  
Yoko Fujita-Yamaguchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Type I Collagen ◽  
Type I ◽  
Collagen Gels

scholarly journals Sulfated Hyaluronan Modulates the Functional Properties and Matrix Effectors Expression of Breast Cancer Cells with Different Estrogen Receptor Status

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1916
Author(s):  
Christos Koutsakis ◽  
Anastasia-Gerasimoula Tavianatou ◽  
Dimitris Kokoretsis ◽  
Georgios Baroutas ◽  
Nikos K. Karamanos
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Functional Properties ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Status ◽  
Migration And Invasion ◽  
Type I ◽  
Mesenchymal Transition

Hyaluronan (HA) is an extracellular matrix glycosaminoglycan (GAG) that plays a pivotal role in breast cancer. While HA is the only GAG not normally substituted with sulfate groups, sulfated hyaluronan (sHA) has previously been used in studies with promising antitumor results. The aim of the present study was to evaluate the effects sHA fragments have on breast cancer cells with different estrogen receptor (ER) status. To this end, ERα-positive MCF-7, and ERβ-positive MDA-MB-231 cells were treated with non-sulfated HA or sHA fragments of 50 kDa. The functional properties of the breast cancer cells and the expression of key matrix effectors were investigated. According to the results, sHA attenuates cell proliferation, migration, and invasion, while increasing adhesion on collagen type I. Furthermore, sHA modulates the expression of epithelial-to-mesenchymal transition (EMT) markers, such as e-cadherin and snail2/slug. Additionally, sHA downregulates matrix remodeling enzymes such as the matrix metalloproteinases MT1-MMP, MMP2, and MMP9. Notably, sHA exhibits a stronger effect on the breast cancer cell properties compared to the non-sulfated counterpart, dependent also on the type of cancer cell type. Consequently, a deeper understanding of the mechanism by which sHA facilitate these processes could contribute to the development of novel therapeutic strategies.

The roles of microRNA-328-3p on proliferation and radiotherapy in breast cancer

2021 ◽  
Author(s):  
Ying Shi ◽  
Pengli Jiang ◽  
Jinqiu Li ◽  
Shengnan Xu ◽  
Bin Liu
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Breast Carcinogenesis ◽  
Aberrant Expression ◽  
Induced Apoptosis ◽  
Cancer Tissues ◽  
The Impact

Abstract Objectives MicroRNAs regulates varieties of molecular pathways and involve in breast carcinogenesis. Here both breast cancer cell lines and human breast cancer tissues were used to investigate the roles of miR-328-3p in breast cancer. Methods The impact of miR-328-3p on proliferation of MDA-MB-231 and T47D cells was determined by MTT assay. transwell migration and matrigel invasion assays were performed to evaluate effects of miR-328-3p on migration and invasion of breast cancer cells. Caspase 3/7 activities were measured to examine the impact of miR-328-3p on radiotherapy-induced apoptosis in breast cancer cells. The possible binding site of miR-328-3p was verified by dual-luciferase reporter assay. Quantitative real-time polymerase chain reaction was performed to detect miR-328-3p expression level in breast cancer tissues. Western blot and immunohistochemical studies were used to examine protein expression in breast cancer cells and breast cancer tissue, respectively. Results miR-328-3p involved growth, migration and invasion in breast cancer cells and was associated with radiotherapy sensitivity. MiR-328-3p enhanced radiation-induced apoptosis in breast cancer cells by regulating BAX and Bcl-2 expression. Meanwhile, aberrant expression of miR-328-3p was associated with altered expression of PTEN and p-AKT in breast cancer cells. Further study showed miR-328-3p bound to 3’-UTR of PTEN. In addition, breast cancer tissues showed higher level of miR-328-3p than normal breast tissue and higher level of miR-328-3p was seen in lower stage in breast cancer. Conclusions miR-328-3p displayed essential functions in breast carcinogenesis and might be used to predict radiotherapy response and prognosis in breast cancer.

The type I collagen induction of MT1-MMP-mediated MMP-2 activation is repressed by αVβ3 integrin in human breast cancer cells

2007 ◽  
Vol 26 (4) ◽  
pp. 291-305 ◽  
Author(s):  
Kulrut Borrirukwanit ◽  
Marc A. Lafleur ◽  
Francesca A. Mercuri ◽  
Tony Blick ◽  
John T. Price ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Type I Collagen ◽  
Type I ◽  
Αvβ3 Integrin ◽  
Human Breast Cancer Cells ◽  
Human Breast

scholarly journals Transcriptomic Response of Breast Cancer Cells MDA-MB-231 to Docosahexaenoic Acid: Downregulation of Lipid and Cholesterol Metabolism Genes and Upregulation of Genes of the Pro-Apoptotic ER-Stress Pathway

2020 ◽  
Vol 17 (10) ◽  
pp. 3746 ◽  
Author(s):  
Benoît Chénais ◽  
Marine Cornec ◽  
Solenne Dumont ◽  
Justine Marchand ◽  
Vincent Blanckaert
Keyword(s):  
Breast Cancer ◽  
Docosahexaenoic Acid ◽  
Er Stress ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Health Concern ◽  
Migration And Invasion ◽  
Transcriptomic Response ◽  
The Impact

Despite considerable efforts in prevention and therapy, breast cancer remains a major public health concern worldwide. Numerous studies using breast cancer cell lines have shown the antiproliferative and pro-apoptotic effects of docosahexaenoic acid (DHA). Some studies have also demonstrated the inhibitory effect of DHA on the migration and invasion of breast cancer cells, making DHA a potential anti-metastatic agent. Thus, DHA has shown its potential as a chemotherapeutic adjuvant. However, the molecular mechanisms triggering DHA effects remain unclear, and the aim of this study was to provide a transcriptomic basis for further cellular and molecular investigations. Therefore, MDA-MB-231 cells were treated with 100 µM DHA for 12 h or 24 h before RNA-seq analysis. The results show the great impact of DHA-treatment on the transcriptome, especially after 24 h of treatment. The impact of DHA is particularly visible in genes involved in the cholesterol biosynthesis pathway that is strongly downregulated, and the endoplasmic reticulum (ER)-stress response that is, conversely, upregulated. This ER-stress and unfolded protein response could explain the pro-apoptotic effect of DHA. The expression of genes related to migration and invasion (especially SERPINE1, PLAT, and MMP11) is also impacted by DHA. In conclusion, this transcriptomic analysis supports the antiproliferative, pro-apoptotic and anti-invasive effects of DHA, and provides new avenues for understanding its molecular mechanisms.

scholarly journals FOXA1 upregulation promotes enhancer and transcriptional reprogramming in endocrine-resistant breast cancer

2019 ◽  
Vol 116 (52) ◽  
pp. 26823-26834 ◽  
Author(s):  
Xiaoyong Fu ◽  
Resel Pereira ◽  
Carmine De Angelis ◽  
Jamunarani Veeraraghavan ◽  
Sarmistha Nanda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Migration And Invasion ◽  
Transcriptional Reprogramming ◽  
The Impact

Forkhead box A1 (FOXA1) is a pioneer factor that facilitates chromatin binding and function of lineage-specific and oncogenic transcription factors. Hyperactive FOXA1 signaling due to gene amplification or overexpression has been reported in estrogen receptor-positive (ER+) endocrine-resistant metastatic breast cancer. However, the molecular mechanisms by which FOXA1 up-regulation promotes these processes and the key downstream targets of the FOXA1 oncogenic network remain elusive. Here, we demonstrate that FOXA1 overexpression in ER+breast cancer cells drives genome-wide enhancer reprogramming to activate prometastatic transcriptional programs. Up-regulated FOXA1 employs superenhancers (SEs) to synchronize transcriptional reprogramming in endocrine-resistant breast cancer cells, reflecting an early embryonic development process. We identify the hypoxia-inducible transcription factor hypoxia-inducible factor-2α (HIF-2α) as the top high FOXA1-induced SE target, mediating the impact of high FOXA1 in activating prometastatic gene sets and pathways associated with poor clinical outcome. Using clinical ER+/HER2−metastatic breast cancer datasets, we show that the aberrant FOXA1/HIF-2α transcriptional axis is largely nonconcurrent with theESR1mutations, suggesting different mechanisms of endocrine resistance and treatment strategies. We further demonstrate the selective efficacy of an HIF-2α antagonist, currently in clinical trials for advanced kidney cancer and recurrent glioblastoma, in reducing the clonogenicity, migration, and invasion of endocrine-resistant breast cancer cells expressing high FOXA1. Our study has uncovered high FOXA1-induced enhancer reprogramming and HIF-2α–dependent transcriptional programs as vulnerable targets for treating endocrine-resistant and metastatic breast cancer.

scholarly journals Comprehensive Analysis of MicroRNA (miRNA) Targets in Breast Cancer Cells

2013 ◽  
Vol 288 (38) ◽  
pp. 27480-27493 ◽  
Author(s):  
Meiyun Fan ◽  
Raisa Krutilina ◽  
Jing Sun ◽  
Aarti Sethuraman ◽  
Chuan He Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Functional Enrichment ◽  
Migration And Invasion ◽  
Integrated Analysis ◽  
Primary Tumors ◽  
Mirna Targets ◽  
The Impact

MicroRNAs (miRNAs) regulate mRNA stability and translation through the action of the RNAi-induced silencing complex. In this study, we systematically identified endogenous miRNA target genes by using AGO2 immunoprecipitation (AGO2-IP) and microarray analyses in two breast cancer cell lines, MCF7 and MDA-MB-231, representing luminal and basal-like breast cancer, respectively. The expression levels of ∼70% of the AGO2-IP mRNAs were increased by DROSHA or DICER1 knockdown. In addition, integrated analysis of miRNA expression profiles, mRNA-AGO2 interaction, and the 3′-UTR of mRNAs revealed that >60% of the AGO2-IP mRNAs were putative targets of the 50 most abundantly expressed miRNAs. Together, these results suggested that the majority of the AGO2-associated mRNAs were bona fide miRNA targets. Functional enrichment analysis uncovered that the AGO2-IP mRNAs were involved in regulation of cell cycle, apoptosis, adhesion/migration/invasion, stress responses (e.g. DNA damage and endoplasmic reticulum stress and hypoxia), and cell-cell communication (e.g. Notch and Ephrin signaling pathways). A role of miRNAs in regulating cell migration/invasion and stress response was further defined by examining the impact of DROSHA knockdown on cell behaviors. We demonstrated that DROSHA knockdown enhanced cell migration and invasion, whereas it sensitized cells to cell death induced by suspension culture, glucose depletion, and unfolding protein stress. Data from an orthotopic xenograft model showed that DROSHA knockdown resulted in reduced growth of primary tumors but enhanced lung metastasis. Taken together, these results suggest that miRNAs collectively function to promote survival of tumor cells under stress but suppress cell migration/invasion in breast cancer cells.

The Impact of Antioxidants from the Diet on Breast Cancer Cells Monitored by Raman Microspectroscopy

2018 ◽  
Vol 16 (2) ◽  
pp. 127-137
Author(s):  
Paula Sofia Coutinho Medeiros ◽  
Ana Lúcia Marques Batista de Carvalho ◽  
Cristina Ruano ◽  
Juan Carlos Otero ◽  
Maria Paula Matos Marques
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Breast Adenocarcinoma ◽  
Coumaric Acid ◽  
Human Breast ◽  
The Impact

Background: The impact of the ubiquitous dietary phenolic compound p-coumaric acid on human breast cancer cells was assessed, through a multidisciplinary approach: Combined biological assays for cytotoxicity evaluation and biochemical profiling by Raman microspectroscopic analysis in cells. </P><P> Methods: Para-coumaric acid was shown to exert in vitro chemoprotective and antitumor activities, depending on the concentration and cell line probed: a significant anti-invasive ability was detected for the triple-negative MDA-MB-231 cells, while a high pro-oxidant effect was found for the estrogen- dependent MCF-7 cells. A striking cell selectivity was obtained, with a more noticeable outcome on the triple-negative MDA-MB-231 cell line. Results: The main impact on the cellular biochemical profile was verified to be on proteins and lipids, thus justifying the compound´s anti-invasive effect and chemoprotective ability. Conclusion: p-Coumaric acid was thus shown to be a promising chemoprotective/chemotherapeutic agent, particularly against the low prognosis triple-negative human breast adenocarcinoma.

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