Abstract P1-06-07: Immune-induced epithelial to mesenchymal transition in inflammatory breast cancer induces unique increases in E-cadherin, adhesion and migration through TNF-a, IL-6 and TGF-b

Breast cancer metastasis is one of the main factors associated with high mortality rates among patients. MicroRNAs (miRNAs) play an important role in gene expression regulation, and are associated with the metastatic process in breast cancer. Melatonin, a hormone secreted mainly in the pineal gland, has several oncostatic effects. The aim of this study was to investigate the action of melatonin in the modulation of miRNA-10a-5p and its association with metastatic mechanisms. We have evaluated the effects of melatonin on cell viability in MDA-MB-468 cell line after 24 hours of treatment. MDA-MB-468 and MDA-MB-231 cells were either transfected with inhibitor of miR-10a, or received a scrambled miRNA sequence as a negative control, then these cells were treated with or without melatonin. Gene expression of miR-10a was verified by real-time PCR. Invasion and migration assay using matrigel inserts were performed. The protein expression was analyzed by western blotting to quantify the epithelial-mesenchymal transition (EMT) markers (E-cadherin, claudin 7, and vimentin) and proliferation marker (PIK3CA). Our results showed that melatonin (1 mM) significantly decreased cell viability, and also affected miR-10a expression, which suppressed cell invasion and migration. Melatonin reduced vimentin and claudin 7 protein expressions, and increased E-cadherin. In contrast, inhibition of miR-10a reduced vimentin and did not modulate claudin 7 and E-cadherin. In conclusion, we demonstrated the effectiveness of melatonin in decreasing miR-10a, affecting invasion and migration, and proteins involved with the EMT process, which supports its potential role in the regulation of metastasis.

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Mechanisms Underlying the Altered Proliferation, Invasion and Migration of Endometrial Carcinoma Cells via Small Interfering RNA Specific Snail-1 Transcription Factor in HEC-1A Cells

10.20944/preprints201907.0105.v1 ◽

2019 ◽

Author(s):

Jun Jiang ◽

Jianfen Wang ◽

Yong Shen ◽

Xuelu Jiang

Keyword(s):

Transcription Factor ◽

Endometrial Carcinoma ◽

Epithelial To Mesenchymal Transition ◽

Migration Ability ◽

Small Interference Rna ◽

Mesenchymal Transition ◽

Migration Assay ◽

Invasion And Migration ◽

And Migration ◽

E Cadherin

Snail-1 is a transcription factor that play a role in the regulation of invasion, and metastasis of malignant cells via modulation of the epithelial-to-mesenchymal transition (EMT) process. Here in the current investigation, we knocked down the expression of Snail-1 through small interference RNA (siRNA) in Endometrial carcinoma (EC) associating cell line, namely HEC-1A, and then assessed the migration and proliferation of the transfected cells. We exerted Snail-1 specific siRNA to transfect the HEC-1A cells. Using quantitative Real-time PCR, the mRNA expression levels of Snail-1, MMP-9, Vimentin, and E-cadherin as well as expression level of miR-34a were measured. In addition, western blotting was carried out to determine the protein level of Snail-1. Using MTT and migration assay, the ability of transfected HEC-1A cells in proliferation and migration was evaluated. Snail-1 mRNA and protein expressions were decreased after transfection of HEC-1A cells. As well transfection caused decreased expression of MMP-9 and vimentin, while the expressions of E-cadherin and miR-34a were increased. Transfection of HEC-1A cells resulted in promoted apoptosis rate and reduced migration ability. EMT of EC tumor cells is partially under the impression of Snail-1, which alters the apoptosis and metastasis of these cells. As a consequence, silencing Snail-1 by siRNA may suggest a potentially promising tool in the EC therapy.

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Abstract P5-05-04: E-Cadherin and Its Proteolytic Fragments Trump Epithelial-Mesenchymal Transition and Function as Dominant Oncogenes in Inflammatory Breast Cancer

10.1158/0008-5472.sabcs10-p5-05-04 ◽

2010 ◽

Author(s):

SH Barsky ◽

Y Ye ◽

Y Xiao ◽

K. Yearsley

Keyword(s):

Breast Cancer ◽

Inflammatory Breast Cancer ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

And Function ◽

E Cadherin

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Induced Tamoxifen Resistance is Mediated by Increased Methylation of E-Cadherin in Estrogen Receptor-Expressing Breast Cancer Cells

Scientific Reports ◽

10.1038/s41598-019-50749-1 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Qi Wang ◽

Melisa Gun ◽

Xing-yu Hong

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Epithelial To Mesenchymal Transition ◽

Breast Cancers ◽

Mesenchymal Transition ◽

Tamoxifen Resistant ◽

Mcf 7 ◽

E Cadherin

Abstract Estrogen receptor-positive breast cancers are treated with tamoxifen, a drug that competitively inhibits the binding of estrogen to its receptor. Resistance to tamoxifen is a major hurdle in effective management of target breast cancer patient population. A number of dynamic changes within the tumor microenvironment, including the phenomenon of epithelial to mesenchymal transition (EMT), determine the response to endocrine therapy. EMT is marked by silencing or suppression of epithelial marker, E-Cadherin and we found significantly down-regulated E-Cadherin, among other epithelial markers, and a significantly up-regulated mesenchymal marker, Twist, among other mesenchymal markers, in a model system that comprised of tamoxifen sensitive MCF-7 cells and their tamoxifen-resistant counterparts, MCF-7-TAM, developed by chronic and escalating exposure of parental cells to tamoxifen. Further, E-cadherin, but not Twist, was differentially expressed in MCF-7-TAM cells because of differential methylation. Treatment with demethylating agent 5-azacytidine increased the expression of E-cadherin thus verifying a role of methylation in its silencing and, moreover, 5-azacytidine treatment also re-sensitized MCF-7-TAM cells to tamoxifen, as evaluated by assays for viability, apoptosis and migration potential. The 5-azacytidine effects were similar to effects of E-cadherin overexpression in MCF-7-TAM cells. This work describes novel mechanism of E-cadherin downregulation in tamoxifen resistant breast cancer cells. Further studies are needed to exploit this information for betterment of breast cancer therapy.

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Histone deacetylase inhibitor entinostat reverses epithelial to mesenchymal transition of breast cancer cells by reversing the repression of E-cadherin

Breast Cancer Research and Treatment ◽

10.1007/s10549-013-2784-7 ◽

2013 ◽

Vol 143 (1) ◽

pp. 99-111 ◽

Cited By ~ 42

Author(s):

Preeti Shah ◽

Yael Gau ◽

Gauri Sabnis

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitor ◽

Breast Cancer Cells ◽

Epithelial To Mesenchymal Transition ◽

Mesenchymal Transition ◽

Deacetylase Inhibitor ◽

E Cadherin

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Breast cancer-associated fibroblasts induce epithelial-to-mesenchymal transition in breast cancer cells

Endocrine Related Cancer ◽

10.1530/erc-12-0227 ◽

2012 ◽

Vol 20 (1) ◽

pp. 1-12 ◽

Cited By ~ 70

Author(s):

Patsy S H Soon ◽

Edward Kim ◽

Cindy K Pon ◽

Anthony J Gill ◽

Katrina Moore ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Epithelial To Mesenchymal Transition ◽

Smooth Muscle Actin ◽

Flow Cytometric Analysis ◽

Cancer Associated Fibroblasts ◽

Mcf7 Cells ◽

Mesenchymal Transition ◽

Functional Changes ◽

E Cadherin

Cancer-associated fibroblasts (CAFs) play a role in tumour initiation and progression, possibly by inducing epithelial-to-mesenchymal transition (EMT), a series of cellular changes that is known to underlie the process of metastasis. The aim of this study was to determine whether CAFs and surrounding normal breast fibroblasts (NBFs) are able to induce EMT markers and functional changes in breast epithelial cancer cells. Matched pairs of CAFs and NBFs were established from fresh human breast cancer specimens and characterised by assessment of CXCL12 levels, α-smooth muscle actin (α-SMA) levels and response to doxorubicin. The fibroblasts were then co-cultured with MCF7 cells. Vimentin and E-cadherin expressions were determined in co-cultured MCF7 cells by immunofluorescence and confocal microscopy as well as by western blotting and quantitative PCR. Co-cultured MCF7 cells were also assessed functionally by invasion assay. CAFs secreted higher levels of CXCL12 and expressed higher levels of α-SMA compared with NBFs. CAFs were also less sensitive to doxorubicin as evidenced by less H2AX phosphorylation and reduced apoptosis on flow cytometric analysis of Annexin V compared with NBFs. When co-cultured with MCF7 cells, there was greater vimentin and less E-cadherin expression as well as greater invasiveness in MCF7 cells co-cultured with CAFs compared with those co-cultured with NBFs. CAFs have the ability to induce a greater degree of EMT in MCF7 cell lines, indicating that CAFs contribute to a more malignant breast cancer phenotype and their role in influencing therapy resistance should therefore be considered when treating breast cancer.

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E2F3 drives the epithelial-to-mesenchymal transition, cell invasion, and metastasis in breast cancer

Experimental Biology and Medicine ◽

10.1177/15353702211035693 ◽

2021 ◽

pp. 153537022110356

Author(s):

Shirley Jusino ◽

Yainyrette Rivera-Rivera ◽

Camille Chardón-Colón ◽

Armando J Ruiz-Justiz ◽

Jaleisha Vélez-Velázquez ◽

...

Keyword(s):

Breast Cancer ◽

Cell Invasion ◽

Epithelial To Mesenchymal Transition ◽

Chromosome Instability ◽

Metastatic Potential ◽

Metastatic Progression ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Tumor Growth And Metastasis ◽

And Migration

E2F3 is a transcription factor that may initiate tumorigenesis if overexpressed. Previously, we demonstrated that E2F3 mRNA is overexpressed in breast cancer and that E2F3 overexpression results in centrosome amplification and unregulated mitosis, which can promote aneuploidy and chromosome instability to initiate and sustain tumors. Further, we demonstrated that E2F3 leads to overexpression of the mitotic regulator Shugoshin-1, which until recently had unknown roles in cancer. This study aims to evaluate the roles of E2F3 and Shugoshin-1 in breast cancer metastatic potential. Here we demonstrated that E2F3 and Shugoshin-1 silencing leads to reduced cell invasion and migration in two mesenchymal triple-negative breast cancer (TNBC) cell lines (MDA-MB-231 and Hs578t). Moreover, E2F3 and Shugoshin-1 modulate the expression of epithelial-to-mesenchymal transition-associated genes such as Snail, E-Cadherin, and multiple matrix metalloproteinases. Furthermore, E2F3 depletion leads to reductions in tumor growth and metastasis in NOD- scid Gamma mice. Results from this study suggest a key role for E2F3 and a novel role for Shugoshin-1 in metastatic progression. These results can further help in the improvement of TNBC targeted therapies by interfering with pathways that intersect with the E2F3 and Shugoshin-1 signaling pathways.

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