scholarly journals MiR-155-mediated loss of C/EBPβ shifts the TGF-β response from growth inhibition to epithelial-mesenchymal transition, invasion and metastasis in breast cancer

Oncogene ◽  
2013 ◽  
Vol 32 (50) ◽  
pp. 5614-5624 ◽  
Author(s):  
J Johansson ◽  
T Berg ◽  
E Kurzejamska ◽  
M-F Pang ◽  
V Tabor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Inhibition ◽  
Epithelial Mesenchymal Transition ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition

scholarly journals Cancer-associated fibroblast-derived exosomal miR-18b promotes breast cancer invasion and metastasis by regulating TCEAL7

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Ziqian Yan ◽  
Zhimei Sheng ◽  
Yuanhang Zheng ◽  
Ruijun Feng ◽  
Qinpei Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Mouse Xenograft Model

AbstractStudies have shown that cancer-associated fibroblasts (CAFs) play an irreplaceable role in the occurrence and development of tumors. Therefore, exploring the action and mechanism of CAFs on tumor cells is particularly important. In this study, we compared the effects of CAFs-derived exosomes and normal fibroblasts (NFs)-derived exosomes on breast cancer cells migration and invasion. The results showed that exosomes from both CAFs and NFs could enter into breast cancer cells and CAFs-derived exosomes had a more enhancing effect on breast cancer cells migration and invasion than NFs-derived exosomes. Furthermore, microRNA (miR)-18b was upregulated in CAFs-derived exosomes, and CAFs-derived exosomes miR-18b can promote breast cancer cell migration and metastasis by specifically binding to the 3′UTR of Transcription Elongation Factor A Like 7 (TCEAL7). The miR-18b-TCEAL7 pathway promotes nuclear Snail ectopic activation by activating nuclear factor-kappa B (NF-κB), thereby inducing epithelial-mesenchymal transition (EMT) and promoting cell invasion and metastasis. Moreover, CAFs-derived exosomes miR-18b could promote mouse xenograft model tumor metastasis. Overall, our findings suggest that CAFs-derived exosomes miR-18b promote nuclear Snail ectopic by targeting TCEAL7 to activate the NF-κB pathway, thereby inducing EMT, invasion, and metastasis of breast cancer. Targeting CAFs-derived exosome miR-18b may be a potential treatment option to overcome breast cancer progression.

scholarly journals Hypoxia-induced TGF-β–RBFOX2–ESRP1 axis regulates human MENA alternative splicing and promotes EMT in breast cancer

NAR Cancer ◽  
2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Neha Ahuja ◽  
Cheemala Ashok ◽  
Subhashis Natua ◽  
Deepak Pant ◽  
Anna Cherian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Alternative Splicing ◽  
Transcriptional Repression ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Global Changes ◽  
Invasion And Metastasis ◽  
New Paradigm ◽  
Mesenchymal Transition ◽  
Splicing Regulator

Abstract Hypoxic microenvironment heralds epithelial–mesenchymal transition (EMT), invasion and metastasis in solid tumors. Deregulation of alternative splicing (AS) of several cancer-associated genes has been instrumental in hypoxia-induced EMT. Our study in breast cancer unveils a previously unreported mechanism underlying hypoxia-mediated AS of hMENA, a crucial cytoskeleton remodeler during EMT. We report that the hypoxia-driven depletion of splicing regulator ESRP1 leads to skipping of hMENA exon 11a producing a pro-metastatic isoform, hMENAΔ11a. The transcriptional repression of ESRP1 is mediated by SLUG, which gets stimulated via hypoxia-driven TGF-β signaling. Interestingly, RBFOX2, an otherwise RNA-binding protein, is also found to transcriptionally repress ESRP1 while interacting with SLUG. Similar to SLUG, RBFOX2 gets upregulated under hypoxia via TGF-β signaling. Notably, we found that the exosomal delivery of TGF-β contributes to the elevation of TGF-β signaling under hypoxia. Moreover, our results show that in addition to hMENA, hypoxia-induced TGF-β signaling contributes to global changes in AS of genes associated with EMT. Overall, our findings reveal a new paradigm of hypoxia-driven AS regulation of hMENA and insinuate important implications in therapeutics targeting EMT.

scholarly journals MicroRNAs regulate the epithelial–mesenchymal transition and influence breast cancer invasion and metastasis

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769168 ◽  
Author(s):  
Min Zhao ◽  
Lin Ang ◽  
Jin Huang ◽  
Jin Wang
Keyword(s):  
Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Invasion ◽  
Invasion And Metastasis ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Rna Molecules ◽  
Breast Cancer Invasion ◽  
Proliferation And Apoptosis ◽  
Post Transcriptional Regulation

MicroRNAs are small RNA molecules that play a major role in the post-transcriptional regulation of genes and influence the development, differentiation, proliferation, and apoptosis of cells and the development and progression of tumors. The epithelial–mesenchymal transition is a process by which epithelial cells morphologically transform into cells with a mesenchymal phenotype. The epithelial–mesenchymal transition plays a highly important role in tumor invasion and metastasis. Increasing evidence indicates that microRNAs are tightly associated with epithelial–mesenchymal transition regulation in tumor cells. In breast cancer, various microRNA molecules have been identified as epithelial–mesenchymal transition inducers or inhibitors, which, through different mechanisms and signaling pathways, participate in the regulation of breast cancer invasion and metastasis among various biological behaviors. The epithelial–mesenchymal transition–related microRNAs in breast cancer provide valuable molecules for researching cell invasion and metastasis, and they also provide candidate targets that may be significant for the targeted therapy of breast cancer.

scholarly journals Heat treatment-induced autophagy promotes invasion and metastasis via TGF-β2 mediated epithelial-mesenchymal transition in breast cancer cells

2021 ◽  
Author(s):  
Zhen-Nan Li ◽  
Cheng Lu ◽  
Feng-Liang Wang ◽  
Hao-Wei Guo ◽  
Zhi-Peng Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heat Treatment ◽  
Tumor Growth ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Autophagy Inhibitor

Abstract Background Insufficient thermal ablation can cause accelerated malignant behaviors and increased metastasis in hepatocellular carcinoma (HCC), and epithelial-mesenchymal transition (EMT) and autophagy are implicated in tumor metastasis. However, whether interactions between autophagy and TGF-β2 induce EMT in breast cancer (BC) after insufficient microwave ablation (MWA) remains unclear. Methods In this study, we treated BC cells with sublethal heat treatment for simulating insufficient MWA, and then the effect of heat treatment on the BC cell phenotypes were explored. CCK-8, colony formation, flow cytometry, transwell and wound healing assays were performed to evaluate the influence of sublethal heat treatment on the proliferation, apoptosis, invasion and migration of BC cells treated with/without autophagy inhibitors. Western blotting, real-time quantitative PCR, immunofluorescence and transmission electron microscopy were carried out to determine the changes of markers associated with autophagy and EMT after sublethal heat treatment. Xenograft models in mice were established by using sublethal heat treated BC cells to investigate the effect of autophagy inhibitor on BC tumor growth in vivo. Results Results showed that heat treatment promoted the proliferation of survived BC cells, which was accompanied by autophagy induction. Heat treatment-induced autophagy up-regulated TGF-β2/Smad2 signaling and promoted phenotype of EMT, thereby enhancing abilities of migration and invasion in BC cells. Increase or decrease of TGF-β2 expression resulted in potentiation and suppression of autophagy as well as enhancement and abatement of EMT. Autophagy inhibitor facilitated apoptosis and repressed proliferation of BC cells in vitro, and thwarted BC cell tumor growth and pulmonary metastasis in vivo. Conclusions This study indicate that heat treatment-induced autophagy promotes invasion and metastasis via TGF-β2/Smad2-mediated EMT. Suppressing autophagy might be a new strategy for overcoming sufficient MWA caused progression and metastasis of residual BC cells.

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