Downregulation of transcription factor Oct4 induces an epithelial-to-mesenchymal transition via enhancement of Ca2+ influx in breast cancer cells

2011 ◽  
Vol 411 (4) ◽  
pp. 786-791 ◽  
Author(s):  
Jiajia Hu ◽  
Kunhua Qin ◽  
Yan Zhang ◽  
Junbo Gong ◽  
Na Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Sodium Channel Nav1.5 Controls Epithelial-to-Mesenchymal Transition and Invasiveness in Breast Cancer Cells Through its Regulation by the Salt-Inducible Kinase-1

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Frédéric Gradek ◽  
Osbaldo Lopez-Charcas ◽  
Stéphanie Chadet ◽  
Lucile Poisson ◽  
Lobna Ouldamer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Voltage Gated Sodium Channels ◽  
Cell Invasiveness ◽  
Mcf 7

AbstractLoss of epithelial polarity and gain in invasiveness by carcinoma cells are critical events in the aggressive progression of cancers and depend on phenotypic transition programs such as the epithelial-to-mesenchymal transition (EMT). Many studies have reported the aberrant expression of voltage-gated sodium channels (NaV) in carcinomas and specifically the NaV1.5 isoform, encoded by the SCN5A gene, in breast cancer. NaV1.5 activity, through an entry of sodium ions, in breast cancer cells is associated with increased invasiveness, but its participation to the EMT has to be clarified. In this study, we show that reducing the expression of NaV1.5 in highly aggressive human MDA-MB-231 breast cancer cells reverted the mesenchymal phenotype, reduced cancer cell invasiveness and the expression of the EMT-promoting transcription factor SNAI1. The heterologous expression of NaV1.5 in weakly invasive MCF-7 breast cancer cells induced their expression of both SNAI1 and ZEB1 and increased their invasive capacities. In MCF-7 cells the stimulation with the EMT-activator signal TGF-β1 increased the expression of SCN5A. Moreover, the reduction of the salt-inducible kinase 1 (SIK1) expression promoted NaV1.5-dependent invasiveness and expression of EMT-associated transcription factor SNAI1. Altogether, these results indicated a prominent role of SIK1 in regulating NaV1.5-dependent EMT and invasiveness.

scholarly journals The Transcription Factor Snail Mediates Epithelial to Mesenchymal Transitions by Repression of Estrogen Receptor-α

2007 ◽  
Vol 21 (12) ◽  
pp. 2907-2918 ◽  
Author(s):  
Archana Dhasarathy ◽  
Masahiro Kajita ◽  
Paul A. Wade
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Dna Sequences ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Phenotypic Properties ◽  
Mesenchymal Transition

Abstract The estrogen receptor (ER)-α (ESR1) is a key regulatory molecule in mammary epithelial cell development. Loss of ER-α in breast cancer is correlated with poor prognosis, increased recurrence after treatment, and an elevated incidence of metastasis. A proposed molecular pathway by which ER-α acts to constrain invasive growth in breast cancer cells involves direct, ER-α-dependent expression of metastasis-associated protein 3, a cell-type-specific component of the Mi-2/NuRD chromatin remodeling complex. MTA3 in turn represses expression of Snail, a transcription factor linked to epithelial to mesenchymal transition and cancer metastasis. To elucidate its role(s) in epithelial to mesenchymal transition (EMT), we expressed Snail in the noninvasive, ER-α-positive MCF-7 cell line. Snail expression led to decreased cell-cell adhesion and increased cell invasiveness. Furthermore, we observed loss of ER-α expression at both the RNA and protein level that was accompanied by direct interaction of Snail with regulatory DNA sequences at the ESR1 locus. A consequence of loss of ER-α function in this system was the increased abundance of key components of the TGF-β signaling pathway. Thus, cross-talk among ER-α, Snail, and the TGF-β pathway appears to control critical phenotypic properties of breast cancer cells.

scholarly journals Metadherin enhances the invasiveness of breast cancer cells by inducing epithelial to mesenchymal transition

2011 ◽  
Vol 102 (6) ◽  
pp. 1151-1157 ◽  
Author(s):  
Xiaoyan Li ◽  
Xiaoli Kong ◽  
Qiang Huo ◽  
Haiyang Guo ◽  
Shi Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Global and gene specific DNA methylation in breast cancer cells was not affected during epithelial-to-mesenchymal transition in vitro

Neoplasma ◽  
2016 ◽  
Vol 63 (06) ◽  
pp. 901-910 ◽  
Author(s):  
B. SMOLKOVA ◽  
S. MIKLIKOVA ◽  
V. HORVATHOVA KAJABOVA ◽  
A. BABELOVA ◽  
N. EL YAMANI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Fluid flow exposure promotes Epithelial-to-Mesenchymal Transition and adhesion of breast cancer cells to endothelial cells

2020 ◽  
Author(s):  
Kenneth F. Fuh ◽  
Robert D. Shepherd ◽  
Jessica S. Withell ◽  
Brayden K. Kooistra ◽  
Kristina D Rinker
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Fluid Flow ◽  
Network Analysis ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Endothelial Monolayer ◽  
Mesenchymal Transition

Abstract Background: Fluid forces are an integral part of the tumor microenvironment through all phases of development and progression. However, it is not well understood how these forces affect key steps in the progression of breast cancer of Epithelial-to-Mesenchymal Transition (EMT) and adhesion to vascular wall endothelial cells. EMT is associated with the progression of most carcinomas through induction of new transcriptional programs within affected epithelial cells, resulting in cells becoming more motile and adhesive to endothelial cells.Methods: MDA-MB-231, SK-BR-3, BT-474, and MCF-7 cells and normal Human Mammary Epithelial Cells (HMECs) were exposed to fluid flow in a parallel-plate bioreactor system. Changes in gene expression were quantified using microarrays and qPCR, gene-gene interactions were elucidated using network analysis, and key modified genes were examined in clinical datasets. Changes in protein expression of key EMT markers between chemically induced EMT and flow-exposed cells were compared in immunocytochemistry assays. Finally, the ability of flow-stimulated and unstimulated cancer cells to adhere to an endothelial monolayer was evaluated in flow and static adhesion experiments.Results: Fluid flow stimulation resulted in upregulation of EMT inducers and downregulation of repressors. Specifically, Vimentin and Snail were upregulated both at the gene and protein expression levels in flow stimulated HMECs, suggesting progression towards an EMT phenotype. Flow-induced overexpression of a panel of cell adhesion genes was also observed. Network analysis revealed genes involved in cell flow responses including FN1, PLAU, and ALCAM. When evaluated in clinical datasets, overexpression of FN1, PLAU, and ALCAM was observed in patients with most subtypes of breast cancer. We also observed increased adhesion of flow-stimulated breast cancer cells compared to unstimulated controls, suggesting an increased potential to form secondary tumors at metastatic sites. Conclusions: This study shows that prolonged fluid force exposure on the order of 1 Pa promotes EMT and adhesion of breast cancer cells to an endothelial monolayer. Further, identified biomarkers were distinctly expressed in patient populations. A better understanding of how biophysical forces such as shear stress affect cellular processes involved in metastatic progression of breast cancer is important for identifying new molecular markers for disease progression, and for predicting metastatic risk.

scholarly journals PKCα Modulates Epithelial-to-Mesenchymal Transition and Invasiveness of Breast Cancer Cells Through ZEB1

2019 ◽  
Vol 9 ◽  
Author(s):  
María Candelaria Llorens ◽  
Fabiana Alejandra Rossi ◽  
Iris Alejandra García ◽  
Mariana Cooke ◽  
Martin C. Abba ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition
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