Lipocalin-2 negatively modulates the epithelial-to-mesenchymal transition in hepatocellular carcinoma through the epidermal growth factor (TGF-beta1)/Lcn2/Twist1 pathway

Hepatology ◽  
2013 ◽  
Vol 58 (4) ◽  
pp. 1349-1361 ◽  
Author(s):  
Yun-Peng Wang ◽  
Goung-Ran Yu ◽  
Mi-Jin Lee ◽  
Sang-Yeop Lee ◽  
In-Sun Chu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epithelial To Mesenchymal Transition ◽  
Lipocalin 2 ◽  
Mesenchymal Transition ◽  
Epidermal Growth

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

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769502 ◽  
Author(s):  
Krisha Desai ◽  
Radhika Aiyappa ◽  
Jyothi S Prabhu ◽  
Madhumathy G Nair ◽  
Patrick Varun Lawrence ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epithelial To Mesenchymal Transition ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Mesenchymal Transition ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth ◽  
Mcf 7

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 epithelial-to-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.

Sign in / Sign up

Export Citation Format

Share Document