CRH suppressed TGFβ1-induced Epithelial–Mesenchymal Transition via induction of E-cadherin in breast cancer cells

2014 ◽  
Vol 26 (4) ◽  
pp. 757-765 ◽  
Author(s):  
Lai Jin ◽  
Jiandong Chen ◽  
Li Li ◽  
Chuanhua Li ◽  
Cheng Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
E Cadherin

scholarly journals P53 Silencing and Mammosphere Formation in Breast Cancer Cells Harbouring P53 Gain-of-Function Mutations Trigger Epithelial-Mesenchymal Transition

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 201s-201s
Author(s):  
Z.Y. Yee ◽  
C.L. Lim ◽  
F.L. Felicia Chung ◽  
C.O. Leong
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
P53 Gene ◽  
Mesenchymal Transition ◽  
Cell Markers ◽  
Emt Markers ◽  
E Cadherin

Background: Mutations in p53 gene are observed in ∼50% of all human cancers. In breast cancer alone, 12%-32% of luminal, 84% of basal-like and 75% of HER-2 expressing tumors have apparent p53 mutations. Tumor cells undergo epithelial-mesenchymal transition (EMT) to metastasise from primary sites to form secondary tumors at distant regions of the body. EMT is a complex biologic phenomenon which governs the transition of cancer cells with epithelial characteristics to mesenchymal traits, gaining new properties such as aggressiveness and invasiveness. Recent studies revealed that mutations in the p53 gene can give rise to alternate functional phenotypes leading to tumor initiation and progression. Aim: The aim of this study is to develop a robust human breast cancer cellular model to investigate p53 gain-of-function (GOF) mutations and EMT as well as evaluating the EMT phenotype associated with these mutations. Methods: Two breast cancer cell lines, namely MDA-MB-468 and HCC38 carrying the R273H and R273L missense mutations, respectively, were subjected to p53 knockdown using shRNA directed against p53 gene through lentiviral vector transduction. The transduced cells were then harvested for Western blotting to evaluate the protein expression of EMT markers which includes E-cadherin, SNAIL, ZEB1 and vimentin compared with the nontransduced control cells. Subsequently, both cell lines were subjected to mammosphere generation and redifferentiation to determine the basal expression of the EMT markers. Results: Silencing of p53 using siRNA in MDA-MB-468 and HCC38 downregulated E-cadherin expressions but upregulated vimentin levels. Furthermore, E-cadherin levels reduced significantly after conversion from adherent parental cells to mammospheres, but rebound upon redifferentiation. Conversely, vimentin was upregulated in mammospheres as compared with the parental and redifferentiated groups. Conclusion: p53 knockdown in breast cancer cells harboring R273H and R273L mutations favor vimentin expression but not E-cadherin, suggesting that p53-GOF mutants are involved in EMT and the development of metastatic tumors. The mammosphere model accurately recapitulates cell plasticity between epithelial and mesenchymal states, as evidenced by the expression of mesenchymal cell markers in the mammospheres, and epithelial cell markers in adherent and redifferentiated cells.

Comprehensive study on cellular morphologies, proliferation, motility, and epithelial–mesenchymal transition of breast cancer cells incubated on electrospun polymeric fiber substrates

2017 ◽  
Vol 5 (14) ◽  
pp. 2588-2600 ◽  
Author(s):  
Ryota Domura ◽  
Rie Sasaki ◽  
Masami Okamoto ◽  
Minoru Hirano ◽  
Katsunori Kohda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Aligned Fibers ◽  
Polymeric Fiber ◽  
Comprehensive Study ◽  
E Cadherin

Aligned fibers substrates caused elongation and alignment of the MDA-MB-231 cells along the fiber directionsviareducing the cell roundness and E-cadherin expression.

scholarly journals FBXL10 promotes EMT and metastasis of breast cancer cells via regulating the acetylation and transcriptional activity of SNAI1

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yangyang Yang ◽  
Binggong Zhao ◽  
Linlin Lv ◽  
Yuxi Yang ◽  
Shujing Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Bioinformatics Analyses ◽  
Positive Role ◽  
Mesenchymal Transition ◽  
E Cadherin

AbstractF-box and leucine-rich repeat protein 10 (FBXL10) has been reported to play a regulatory role in the initiation and development of breast cancer. Bioinformatics analyses revealed that FBXL10 may involve in the process of cytoskeleton organization. This research aimed to investigate the function of FBXL10 in epithelial-mesenchymal transition (EMT) and metastasis of breast cancer, and tried to reveal the molecular mechanism involved in this issue. Functional experiments in vitro revealed that FBXL10 promoted the migration and invasion of breast cancer cells through inhibiting E-cadherin expression and inducing EMT. Mechanical studies revealed that FBXL10 could specifically interact with SNAI1, but not Slug or ZEB1. And it promoted the transcriptional repression activity of SNAI1 on CDH1 in breast cancer cells. Furthermore, FBXL10 had a positive role for the deacetylation of SNAI1 by facilitating the interaction between SNAI1 and HDAC1, a dominating deacetylase of SNAI1. And the deacetylated SNAI1 showed a more suppressive ability to inhibit the transcription of E-cadherin. Moreover, mouse models were also conducted to confirm the effect of FBXL10 on the lung metastasis of breast cancer in vivo. Totally, our data revealed that FBXL10 served as a pro-metastatic factor in breast cancer via repressing the expression of E-cadherin and inducing EMT. It may provide a novel regulatory axis in the EMT of breast cancer.

scholarly journals A Ca2+-ATPase Regulates E-cadherin Biogenesis and Epithelial–Mesenchymal Transition in Breast Cancer Cells

2019 ◽  
Vol 17 (8) ◽  
pp. 1735-1747 ◽  
Author(s):  
Donna K. Dang ◽  
Monish Ram Makena ◽  
José P. Llongueras ◽  
Hari Prasad ◽  
Myungjun Ko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
E Cadherin

scholarly journals FOXA2-Interacting FOXP2 Prevents Epithelial-Mesenchymal Transition of Breast Cancer Cells by Stimulating E-Cadherin and PHF2 Transcription

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuxiang Liu ◽  
Taolin Chen ◽  
Mingyue Guo ◽  
Yu Li ◽  
Qian Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Language Learning ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mass Spectrometry Analysis ◽  
Mesenchymal Transition ◽  
Spectrometry Analysis ◽  
E Cadherin

FOXP2, a member of forkhead box transcription factor family, was first identified as a language-related gene that played an important role in language learning and facial movement. In addition, FOXP2 was also suggested regulating the progression of cancer cells. In previous studies, we found that FOXA2 inhibited epithelial-mesenchymal transition (EMT) in breast cancer cells. In this study, by identifying FOXA2-interacting proteins from FOXA2-pull-down cell lysates with Mass Spectrometry Analysis, we found that FOXP2 interacted with FOXA2. After confirming the interaction between FOXP2 and FOXA2 through Co-IP and immunofluorescence assays, we showed a correlated expression of FOXP2 and FOXA2 existing in clinical breast cancer samples. The overexpression of FOXP2 attenuated the mesenchymal phenotype whereas the stable knockdown of FOXP2 promoted EMT in breast cancer cells. Even though FOXP2 was believed to act as a transcriptional repressor in most cases, we found that FOXP2 could activate the expression of tumor suppressor PHF2. Meanwhile, we also found that FOXP2 could endogenously bind to the promoter of E-cadherin and activate its transcription. This transcriptional activity of FOXP2 relied on its interaction with FOXA2. Furthermore, the stable knockdown of FOXP2 enhanced the metastatic capacity of breast cancer cells in vivo. Together, the results suggested that FOXP2 could inhibit EMT by activating the transcription of certain genes, such as E-cadherin and PHF2, in concert with FOXA2 in breast cancer cells.

scholarly journals miR-448 inhibits the epithelial-mesenchymal transition in breast cancer cells by directly targeting the E-cadherin repressor ZEB1/2

2018 ◽  
Vol 243 (5) ◽  
pp. 473-480 ◽  
Author(s):  
Peng Ma ◽  
Kan Ni ◽  
Jing Ke ◽  
Wenyi Zhang ◽  
Ying Feng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Rt Pcr ◽  
Mesenchymal Transition ◽  
E Cadherin

Recently, accumulating evidence provides that dysregulation of microRNAs (miRNAs) is considered to play vital roles in tumor progression. Based on microRNA arrays, we found that microRNA-448 (miR-448) was significantly downregulated in breast cancer tissue specimens. In our study, we were in an effort to clarify the function, the direct target gene, and the molecular mechanisms of miR-448 in breast cancer. By quantitative RT–PCR, we analyzed the expression of miR-448 in 16 patients with BC. Overexpression of miR-448 was established by transfecting miR-448-mimics into MDA-MB-231 and MCF-7 cells, methyl thiazolyl- tetrazolium and colony formation assays were performed to evaluate its effects on cell proliferation. We also performed cell migration and invasion assays in breast cells overexpressing miRNA-448. All the results indicated that overexpression of miR-448 in breast cancer cells markedly suppressed cell proliferation, migration, and invasion. Through the quantitative RT–PCR and Western Blots, we also evaluated epithelial–mesenchymal transition. We found that overexpression of miR-448 also downregulated the expression of vimentin, a well-known mesenchymal marker. Meanwhile, the epithelial marker E-cadherin was unregulated, suggesting that miR-448 inhibited epithelial–mesenchymal transition . Bioinformatics assay coupled with Western Blot and luciferase assays revealed that miR-448 directly binds to the 3′UTR of E-cadherin repressor ZEB1/2, resulting in suppression of epithelial–mesenchymal transition in breast cancer cells. Impact statement In our study, we revealed that miR-448 played a vital role in breast cancer development and we also uncovered the mechanisms of it. Following is the short description of the main findings: miR-448 is downregulated in BC. miR-448 regulates cell proliferation, migration, and invasion in BC. miR-448 specifically regulates ZEB1/2  through binding to the 3′UTR in BC cells. miR-448 inhibits cell migration, invasion,  and EMT by targeting to the 3′UTR of  ZEB1/2.

scholarly journals A Ca2+-ATPase Regulates E-cadherin Biogenesis and Epithelial-Mesenchymal Transition in Breast Cancer Cells

2018 ◽  
Author(s):  
Donna K. Dang ◽  
Monish Ram Makena ◽  
José P. Llongueras ◽  
Hari Prasad ◽  
Myungjun Ko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Adhesion ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Cancer ◽  
Benign Tumors ◽  
Mesenchymal Transition ◽  
E Cadherin

AbstractProgression of benign tumors to invasive, metastatic cancer is accompanied by the epithelial to mesenchymal transition (EMT), characterized by loss of the cell-adhesion protein E-cadherin. Although silencing mutations and transcriptional repression of the E-cadherin gene have been widely studied, not much is known about post-translational regulation of E-cadherin in tumors. We show that E-cadherin is tightly co-expressed with the secretory pathway Ca2+-ATPase isoform 2, SPCA2 (ATP2C2), in breast tumors. Loss of SPCA2 impairs surface expression of E-cadherin and elicits mesenchymal gene expression through disruption of cell adhesion in tumorspheres and downstream Hippo-YAP signaling. Conversely, ectopic expression of SPCA2 in triple negative breast cancer (TNBC) elevates baseline Ca2+ and YAP phosphorylation, enhances post-translational expression of E-cadherin, and suppresses mesenchymal gene expression. Thus, loss of SPCA2 phenocopies loss of E-cadherin in the Hippo signaling pathway and EMT-MET transitions, consistent with a functional role for SPCA2 in E-cadherin biogenesis. Furthermore, we show that SPCA2 suppresses invasive phenotypes, including cell migration in vitro and tumor metastasis in vivo. Based on these findings, we propose that SPCA2 functions as a key regulator of EMT and may be a potential therapeutic target for treatment of metastatic cancer.ImplicationsPost-translational control of E-cadherin and the Hippo pathway by calcium signaling regulates epithelial mesenchymal transition in breast cancer cells.

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