Consequently, our research revealed a new ZEB1-hTERT signaling pathway involved in cell proliferation regulation that has never before been illuminated in breast cancer.
Consistent with the fact that higher level of deltaEF1 expression is associated with more invasive phenotype of breast cancer cells, our collective data suggests that deltaEF1 is likely the switch through which BMP-6 restores E-cadherin-mediated cell-to-cell adhesion and prevents breast cancer metastasis.
E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells.
Enhanced expression of genes associated with a mesenchymal transition includes ZEB1/2, TWIST, and FOXC1. miRNAs are known regulators of gene expression and altered miRNA expression is known to enhance EMT in breast cancer.
Finally, multivariate survival analysis reveals that ZEB1 and its expression signature are significantly associated with reduced overall survival in breast cancer patients.
Furthermore, we identified that miR-708-3p inhibits breast cancer cell epithelial-to-mesenchymal transition (EMT) by directly targeting EMT activators, including ZEB1, CDH2 and vimentin.
In addition, the association between BCL6, ZEB1 and ZEB2 expression and the clinicopathological characteristics and survival of patients with breast cancer were analyzed.
In MDA-MB-231 cells, down-regulated lncRNA-ROR could inhibit the EMT of breast cancer cells and enhance the sensibility of breast cancer cells to tamoxifen by increasing miR-205 expression and suppressing the expressions of ZEB1 and ZEB2.
In this study, while interrogating human databases, we uncover a remarkable decrease in relapse-free survival of breast cancer patients expressing high ZEB1 levels in the stroma.
Indeed, we observed an inverse relation between MYB and ZEB1 expression in two in vitro EMT cell models, in matched human breast tumors and lymph node metastases, and in human breast cancer cell lines.
Knockdown of ZEB1 suppressed the formation of vasculogenic mimicry and epithelial-mesenchymal transition in the human breast cancer cell line MDA-MB-231.