HR+HER2− breast cancers with growth factor receptor–mediated EMT have a poor prognosis and lapatinib downregulates EMT in MCF-7 cells

Abstract

Despite an overall good prognosis, a significant proportion of patients with hormone receptor positive human epidermal growth factor receptor 2 negative breast cancers develop distant metastases. The metastatic potential of epithelial cells is known to be regulated by tumor-stromal interaction and mediated by epithelial-to-mesenchymal transition. Hormone receptor positive human epidermal growth factor receptor 2 negative tumors were used to estimate markers of epithelialto-mesenchymal transition, and the luminal breast cancer cell line MCF-7 was used to examine the interactions between integrins and growth factor receptors in causation of epithelial-to-mesenchymal transition. A total of 140 primary tumors were sub-divided into groups enriched for the markers of epithelial-to-mesenchymal transition (snail family transcriptional repressor 2 and integrin β6) versus those with low levels. Within the epithelial-to-mesenchymal transition+ tumors, there was a positive correlation between the transcripts of integrin β6 and growth factor receptors-human epidermal growth factor receptor 2 and epidermal growth factor receptor. In tumors enriched for epithelial-to-mesenchymal transition markers, patients with tumors with the highest quartile of growth factor receptor transcripts had a shorter disease-free survival compared to patients with low growth factor receptor expression by Kaplan-Meier analysis (log rank, p = 0.03). Epithelial-to-mesenchymal transition was induced in MCF-7 cells by treatment with transforming growth factor beta 1 and confirmed by upregulation of SNAI1 and SNAI2 transcripts, increase of vimentin and integrin β6 protein, and repression of E-cadherin. Treatment of these cells with the dual-specificity tyrosine-kinase inhibitor lapatinib led to downregulation of epithelial-to-mesenchymal transition as indicated by lower levels of SNAI1 and SNAI2 transcripts, integrin αvβ6, and matrix metalloproteinase 9 protein. The results suggest that synergistic interactions between growth factor receptors and integrin β6 could mediate epithelial-to-mesenchymal transition and migration in a subset of luminal breast cancers and lapatinib might be effective in disrupting this interaction.

Human iPSC gene signatures and X chromosome dosage impact response to WNT inhibition and cardiac differentiation fate

“…Additionally, we found that ELK1 targets are overexpressed in CM-fated iPSCs, which is consistent with previous studies showing that knockdown of ELK1 in immortalized human bronchial epithelial cells, small airway epithelial cells, and luminal breast cancer cell line (MCF-7) is associated with increased EMT (Desai et al, 2017;Tatler et al, 2016).…”

Epithelial Mesenchymal Transition (EMT) in Metastatic Breast Cancer in Omani Women

“…Circulating tumor cells (CTC) that show an EMT signature could form an early metastatic alert [69] or serve to detect minimal residual disease after therapy [70]. In an in vitro study on luminal breast cancer MCF-7 cell lines developing EMT expression induced by transcription factors, Lapitinib administration was shown to downregulate EMT expression [71]. Additionally, newer therapies may complement or supplement existing modalities improving patient outcome especially in poor-prognosis subsets of breast cancer.…”

The LQB-223 Compound Modulates Antiapoptotic Proteins and Impairs Breast Cancer Cell Growth and Migration

“…Here, we used cell lines with different metastatic potentials; the MDA-MB-231 line is a highly invasive and metastatic triple-negative model, whereas MCF-7 is a luminal non-invasive breast cancer cell line model [20,21]. The expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal receptor (HER) in breast tumors plays a role in crucial cellular events, like chemoresistance and invasiveness [22]. In addition, MCF-7 presents wild-type p53 protein, while MDA-MB-231 harbors mutant p53 with loss-of-function which confers poor prognosis and contributes to the MDR phenotype observed in some breast cancers [23].…”