scholarly journals Nuclear Phosphatidylinositol-Phosphate Type I Kinase α-Coupled Star-PAP Polyadenylation Regulates Cell Invasion

2017 ◽  
Vol 38 (5) ◽  
Author(s):  
Sudheesh A.P. ◽  
Rakesh S. Laishram
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Invasion ◽  
Breast Cancer Cells ◽  
Type I ◽  
Dependent Manner ◽  
Mcf7 Cells ◽  
Phosphatidylinositol Phosphate ◽  
Invasive Mechanism ◽  
Cellular Invasiveness

ABSTRACTStar-PAP, a nuclear phosphatidylinositol (PI) signal-regulated poly(A) polymerase (PAP), couples with type I PI phosphate kinase α (PIPKIα) and controls gene expression. We show that Star-PAP and PIPKIα together regulate 3′-end processing and expression of pre-mRNAs encoding key anti-invasive factors (KISS1R,CDH1,NME1,CDH13,FEZ1, andWIF1) in breast cancer. Consistently, the endogenous Star-PAP level is negatively correlated with the cellular invasiveness of breast cancer cells. While silencing Star-PAP or PIPKIα increases cellular invasiveness in low-invasiveness MCF7 cells, Star-PAP overexpression decreases invasiveness in highly invasive MDA-MB-231 cells in a cellular Star-PAP level-dependent manner. However, expression of the PIPKIα-noninteracting Star-PAP mutant or the phosphodeficient Star-PAP (S6A mutant) has no effect on cellular invasiveness. These results strongly indicate that PIPKIα interaction and Star-PAP S6 phosphorylation are required for Star-PAP-mediated regulation of cancer cell invasion and give specificity to target anti-invasive gene expression. Our study establishes Star-PAP–PIPKIα-mediated 3′-end processing as a key anti-invasive mechanism in breast cancer.

scholarly journals Identification of drivers of breast cancer invasion by secretome analysis: insight into CTGF signaling

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Johanna W. Hellinger ◽  
Franziska Schömel ◽  
Judith V. Buse ◽  
Christof Lenz ◽  
Gerd Bauerschmitz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Transforming Growth Factor Beta ◽  
Breast Cancer Cells ◽  
Transforming Growth Factor ◽  
Tissue Growth ◽  
Dependent Manner ◽  
Mesenchymal Transition

Abstract An altered consistency of tumor microenvironment facilitates the progression of the tumor towards metastasis. Here we combine data from secretome and proteome analysis using mass spectrometry with microarray data from mesenchymal transformed breast cancer cells (MCF-7-EMT) to elucidate the drivers of epithelial-mesenchymal transition (EMT) and cell invasion. Suppression of connective tissue growth factor (CTGF) reduced invasion in 2D and 3D invasion assays and expression of transforming growth factor-beta-induced protein ig-h3 (TGFBI), Zinc finger E-box-binding homeobox 1 (ZEB1) and lysyl oxidase (LOX), while the adhesion of cell-extracellular matrix (ECM) in mesenchymal transformed breast cancer cells is increased. In contrast, an enhanced expression of CTGF leads to an increased 3D invasion, expression of fibronectin 1 (FN1), secreted protein acidic and cysteine rich (SPARC) and CD44 and a reduced cell ECM adhesion. Gonadotropin-releasing hormone (GnRH) agonist Triptorelin reduces CTGF expression in a Ras homolog family member A (RhoA)-dependent manner. Our results suggest that CTGF drives breast cancer cell invasion in vitro and therefore could be an attractive therapeutic target for drug development to prevent the spread of 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.

Differential Procoagulant Phenotype of Pancreatic and Breast Cancer Cells Related to Different Tissue Factor Activity.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3992-3992
Author(s):  
Grigoris T. Gerotziafas ◽  
Ismail Elalamy ◽  
Marie-Paule Roman ◽  
Claudine Prengel ◽  
Elisabeth Verdy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tissue Factor ◽  
Breast Cancer Cells ◽  
Thrombin Generation ◽  
Human Platelet ◽  
Procoagulant Activity ◽  
Dependent Manner ◽  
Mcf7 Cells ◽  
Platelet Poor Plasma

Abstract Tissue factor (TF) expressed by some cancer cells is implicated in metastasis and angiogenesis. The influence of cancer cells on blood coagulation has not been adequately studied. We evaluated the procoagulant potential of pancreatic and breast cancer cells (BXPC3 and MCF7 cell lines respectively) when they are in contact with human platelet-poor plasma (PPP). At 40% and 90% confluence, adhesive cultures of BXPC3 and MCF7 cells were treated with trypsine according to standardized procedure and cancer cells were suspended in normal human platelet poor plasma (PPP) at increasing concentrations. Coagulation was triggered by CaCl2 addition and thrombin generation (TG) was monitored using the Calibrated Automated Thrombogram-Thrombinoscope® (Biodis-France). In some experiments, cancer cells were incubated for 30 min with a polyclonal specific anti-TF antibody (American Diagnostics). Cancer cells accelerated TG by decreasing significantly lag-time, and time to Peak of thrombin (ttPeak) but they did not significantly influence the endogenous thrombin potential. BXPC3 had significantly more potent procoagulant activity compared to MCF7 cells. Incubation of cancer cells with anti-TF antibody resulted in a concentration dependent inhibition of their procoagulant effect. The IC50 of the anti-TF antibody for TG induced by BXPC3 was about 10-fold higher to that for MCF7. Pancreatic cancer cells (BXPC3) and breast cancer cells (MCF7) accelerate thrombin generation of human plasma in a TF-dependent manner. BXPC3 have more potent procoagulant activity than MCF7 probably due to increased TF expression.

scholarly journals Rac1 and Stathmin but Not EB1 Are Required for Invasion of Breast Cancer Cells in Response to IGF-I

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Shigeru Morimura ◽  
Kazuhide Takahashi
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Invasion ◽  
Breast Cancer Cells ◽  
Regulatory Protein ◽  
Leading Edge ◽  
Mcf7 Cells ◽  
Igf I ◽  
Interfering Rna ◽  
Lamellipodia Formation

Cell migration is considered necessary for the invasion that accompanies the directional formation of the cellular protrusions termed lamellipodia. In invasive breast cancer MDA-MB-231 cells, lamellipodia formation is preceded by translocation of the actin cytoskeletal regulatory protein WAVE2 to the leading edge. WAVE2 translocation and lamellipodia formation require many signaling molecules, including PI3K, Rac1, Pak1, IRSp53, stathmin, and EB1, but whether these molecules are necessary for invasion remains unclear. In noninvasive breast cancer MCF7 cells, no lamellipodia were induced by IGF-I, whereas in MDA-MB-231 cells, Rac1, stathmin, and EB1 were overexpressed. Depletion of Rac1 or stathmin by small interfering RNA abrogated the IGF-I-induced invasion of MDA-MB-231 cells; however, depletion of EB1 did not, indicating the necessity of Rac1 and stathmin but not EB1 for invasion. The signaling pathway leading to cell invasion may not be identical but shares some common molecules, leading to cell migration through lamellipodia formation.

scholarly journals Quercetin Potentiates the Chemosensitivity of Human Breast Cancer Cells to 5-Fluorouracil

2021 ◽  
Author(s):  
Fatemeh Mawalizadeh ◽  
Ghorban Mohammadzadeh ◽  
azam khedri ◽  
mojtaba rashidi
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Colony Formation ◽  
Breast Cancer Cells ◽  
In Vivo Studies ◽  
Mcf7 Cells ◽  
Chemotherapy Drugs ◽  
Apoptotic Effect

Abstract Background: breast cancer is one of the leading causes of cancer mortality worldwide. 5-fluorouracil (5-FU) is one of the chemotherapy drugs to treat breast cancer, but it is associated with several side effects. Combination therapy is a way to increase the effectiveness of chemo drugs and decrease their usage dose. Quercetin (Quer) is one of the natural polyphenols with anti-cancer properties. This study investigated the apoptotic effect of 5-FU in combination with Quer compared with 5-FU alone on MCF7 breast cancer cells.Method and Results: Different single and combined concentrations of 5-FU and Quer were applied to MCF 7 cells for 48 hours. Cell viability, apoptosis, gene expression of Bax and Bcl2, and colony number were assessed using MTT assay, flow cytometry, quantitative real-time PCR, and Colony formation assay, respectively. The combination of 5-FU and Quer compared to 5-FU alone improved apoptosis by increasing and decreasing the gene expression of Bax and Bcl2, respectively, and decreased colony formation in MCF7 cells.Conclusion: Quer potentiates the sensitivity of breast cancer to 5-FU so that this combination may be proposed as a treatment for breast cancer. Therefore, this combination can be suggested for future in vivo studies.

scholarly journals FOXP3 Activates SUMO-Conjugating UBC9 Gene in MCF7 Breast Cancer Cells

2018 ◽  
Vol 19 (7) ◽  
pp. 2036
Author(s):  
Chiung-Min Wang ◽  
William Yang ◽  
Runhua Liu ◽  
Lizhong Wang ◽  
Wei-Hsiung Yang
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Treg Cells ◽  
Site Directed Mutagenesis ◽  
Hek293 Cells ◽  
Dependent Manner ◽  
Post Translational Modification ◽  
Mcf7 Cells ◽  
Dose Dependent

Forkhead Box Protein P3 (FOXP3), a transcription factor of the FOX protein family, is essentially involved in the development of regulatory T (Treg) cells, and functions as a tumor suppressor. Although FOXP3 has been widely studied in immune system and cancer development, its function in the regulation of the UBC9 gene (for the sole E2 enzyme of SUMOylation) is unknown. Herein, we find that the overexpression of FOXP3 in human MCF7 breast cancer cells increases the level of UBC9 mRNA. Moreover, the level of UBC9 protein dose-dependently increases in the FOXP3-Tet-off MCF7 cells. Notably, the promoter activity of the UBC9 is activated by FOXP3 in a dose-dependent manner in both the MCF7 and HEK293 cells. Next, by mapping the UBC9 promoter as well as the site-directed mutagenesis and ChIP analysis, we show that the FOXP3 response element at the −310 bp region, but not the −2182 bp region, is mainly required for UBC9 activation by FOXP3. Finally, we demonstrate that the removal of phosphorylation (S418A and Y342F) and the removal of acetylation/ubiquitination (K263R and K263RK268R) of the FOXP3 result in attenuated transcriptional activity of UBC9. Taken together, FOXP3 acts as a novel transcriptional activator of the human UBC9 gene, suggesting that FOXP3 may have physiological functions as a novel player in global SUMOylation, as well as other post-translational modification systems.

scholarly journals The conformation of the estrogen receptor directs estrogen-induced apoptosis in breast cancer: a hypothesis

2011 ◽  
Vol 5 (1) ◽  
Author(s):  
Philipp Maximov ◽  
Surojeet Sengupta ◽  
Joan S. Lewis-Wambi ◽  
Helen R. Kim ◽  
Ramona F. Curpan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Binding Mode ◽  
Type I ◽  
Mcf7 Cells ◽  
Protein Levels ◽  
Induced Apoptosis

Abstract: Estrogens are classified as type I (planar) and type II (angular) based on their structures. In this study, we used triphenylethylenes (TPEs) compounds related to 4-hydroxytamoxifen 4OHT to address the hypothesis that the conformation of the liganded estrogen receptor (ERα) can dictate the E2-induced apoptosis of the ER+ breast cancer cells.: ERα positive MCF7:5C cells were used to study apoptosis induced by E2, 4OHT and TPEs. Growth and apoptosis assays were used to evaluate apoptosis and the ability to reverse E2-induced apoptosis. ERα protein was measured by Western blotting to investigate the destruction of ERα by TPEs in MCF7 cells. Chromatin immunoprecipitation (ChIP) assays were performed to study the in vivo recruitment of ERα and SRC3 at classical E2-responsive promoter TFF1 (PS2) by TPEs. Molecular modeling was used to predict the binding mode of the TPE to the ERα.: TPEs were not only unable to induce efficient apoptosis in MCF7:5C cells but also reversed the E2-induced apoptosis similar to 4OHT. Furthermore, the TPEs and 4OHT did not reduce the ERα protein levels unlike E2. ChIP assay confirmed very weak recruitment of SRC3 despite modest recruitment of ERα in the presence of TPEs. Mole-ular modeling suggests that TPE would bind in antagonistic mode with ERα.: Our results advances the hypothesis that the TPE liganded ERα complex structurally resembles the 4OHT bound ERα and cannot efficiently recruit co-activator SRC3. As a result, the TPE complex cannot induce apoptosis of ER+ breast cancer cells, although it can cause growth of the breast cancer cells. The conformation of the estrogen-ER complex differentially controls growth and apoptosis.

scholarly journals Glycyrrhizin inhibits the invasion and metastasis of breast cancer cells via upregulation of expressions of miR-200c and e-cadherin

2020 ◽  
Vol 19 (9) ◽  
pp. 1807-1813
Author(s):  
Lihong He ◽  
Xiaorui Wang ◽  
Qing Ma ◽  
Weipeng Zhao ◽  
Yongsheng Jia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Breast Cancer Cells ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Invasion And Metastasis ◽  
Concentration Dependent Manner ◽  
Significant Difference ◽  
E Cadherin

Purpose: To determine the inhibitory effect of glycyrrhizin (GLA) on cell invasion and metastasis in mammary carcinoma cells, and the mechanisms of actions involved.Methods: The effect of GLA at different concentrations on proliferation of breast cancer MDA-MB-231 and BT549 cells was assayed by MTT method. Transwell assay was used to determine the effect of GLA at different concentrations on invasiveness and metastasis of breast cancer MDA-MB-231 and BT549 cells. The influence of LGA on expressions of microRNA-200c and miR-200c was assayed by reverse transcriptase-polymerase chain reaction (RT-PCR).Results: There was no statistically significant difference in cell proliferation amongst cells treated with 5 and 20 μM GLA and untreated breast cancer cells. However, the proliferation of cells treated with 40 μM GLA was significantly reduced (p < 0.05). In the cell invasion and migration experiments, cell population transferred to the base of Transwell chamber in the two cell lines treated with GLA was markedly decreased, relative to cells without GLA treatment, while the number of cells decreased with increase in GLA concentration (p < 0.05). Results from image-pro-plus analysis revealed that the population of cells quantitatively crossing the Transwell compartment membrane decreased with increase in GLA concentration (p < 0.05). The expression of e-cadherin was increased by GLA treatment in a concentration-dependent manner. Moreover, GLA treatment led to significant changes in amounts of miR-200s a, b and c, with changes in miR-200c being the most significant (p < 0.05).Conclusion: GLA suppresses the invasiveness and metastasis of breast cancer MDA-MB-231 and BT549 cells via upregulation of the expressions of miR-200c and e-cadherin. These findings provide a theoretical basis for the development of new breast cancer drugs. Keywords: Glycyrrhiza, GLA, miR-200c, E-cadherin, Inhibition, Breast cancer cells, Invasion, Metastasis

Sign in / Sign up

Export Citation Format

Share Document