HER2 and β-catenin protein location: importance in the prognosis of breast cancer patients and their correlation when breast cancer cells suffer stressful situations

Abstract

In human breast cancer, β-catenin localization has been related with disease prognosis. Since HER2-positive patients are an important subgroup, and that in breast cancer cells a direct interaction of β-catenin/HER2 has been reported, in the present study we have explored whether β-catenin location is related with the disease survival. The study was performed in a tumor bank from patients (n = 140) that did not receive specific anti-HER2 therapy. The proteins were detected by immunohistochemistry in serial sections, 47 (33.5%) patients were HER2-positive with a long follow-up. HER2-positive patients that displayed β-catenin at the plasma membrane (completely surrounding the tumour cells) showed a significant better disease-free survival and overall survival than the patients showing the protein on other locations. Then we explored the dynamics of the co-expression of β-catenin and HER2 in human MCF-7 and SKBR3 cells exposed to different stressful situations. In untreated conditions MCF-7 and SKBR3 cells showed very different β-catenin localization. In MCF-7 cells, cadmium administration caused a striking change in β-catenin localization driving it from plasma membrane to cytoplasmic and perinuclear areas and HER2 showed a similar localization patterns. The changes induced by cadmium were compared with heat shock, H2O2 and tamoxifen treatments. In conclusion, this study shows the dynamical associations of HER2 and β-catenin and their changes in subcellular localizations driven by stressful situations. In addition, we report for the first time the correlation between plasma membrane associated β-catenin in HER2-positive breast cancer and survival outcome, and the importance of the protein localization in breast cancer samples.

The role of circulating extracellular vesicles in breast cancer classification and molecular subtyping

“…[9][10][11] Our results show that PAI-1, ADAM12, and β-catenin are more abundant in advanced stages compared to primary tumors. Our results correlated with in vivo and in vitro studies conducted previously [12][13][14] using cells and tumor tissues.…”

Baicalin inhibits the metastasis of highly aggressive breast cancer cells by reversing epithelial-to-mesenchymal transition by targeting β-catenin signaling

“…Upon Wnt ligand engagement, β-catenin is activated and disrupted, followed by its translocation from the cytoplasm into the nucleus, where it facilitates the transcription of genes involved in EMT, such as Twist, Snail, Slug, which repress the expression of E-cadherin, influencing cell junction and polarity (37). Previous studies have reported that overexpression and hyperactivation of β-catenin are observed in aggressive basallike breast cancer, and are positively correlated with poor patient clinical outcome (38)(39)(40). Therefore, β-catenin may be a novel therapeutic target with which to overcome breast cancer metastasis and improve the prognosis of breast cancer patients.…”

Evaluation of expression of the Wnt signaling components in canine mammary tumors via RT2 Profiler PCR Array and immunochemistry assays

“…In addition, we did not detect a correlation between the intensity of β-catenin expression and the survival period of CMT patients (data not shown). Concerning the inconsistencies among previous reports on the correlation between the expression and subcellular location of β-catenin and the prognosis of human breast cancer and CMTs [ 3 4 13 14 ], further studies are required to understand the roles played by β-catenin in the tumorigenesis and tumor progression of CMTs.…”