Insights on possible interplay between epithelial-mesenchymal transition and T-type voltage gated calcium channels genes in metastatic breast carcinoma

Abstract

Breast cancer (BC) is the most common life-threatening malignancy amongst women with high incidence worldwide. In Egypt, it is the most known malignancy amongst females. Epithelial-mesenchymal transition (EMT) participates in breast tumors’ invasiveness, and metastasis, but the process is poorly understood. The involvement of voltage-gated calcium channels signaling in EMT has not yet been fully explored. Therefore, the aim of this study was to investigate the possible role of T-type calcium channels in metastasis and EMT among breast cancer patients. The study was carried out on 48 female breast cancer patients who were divided into two groups; metastatic and non-metastatic. qRT-PCR was employed to measure the expression of EMT marker genes (N- cadherin, E-cadherin, Snail, Vimentin and T-type VGCCs genes (CACNA1G, CACNA1H, and CACNA1I). The results of the present study revealed differential expression of the EMT marker genes in blood and tissue of non-metastatic and metastatic breast cancer patients, with a clear tendency for the mesenchymal markers to be significantly elevated in metastatic patients as well as malignant tissues taken from non-metastatic patients as compared to their paired tumor adjacent normal (TAN) tissue. Both CACNA1H and CACNA1I (T-type VGCCs oncogenes) were significantly elevated in blood of metastatic patients when compared to non-metastatic ones. In contrast, CACNA1G (tumor suppressor) exhibited a significant decrease in metastatic patients. The strong correlation between the expression of T-type VGCCs and mesenchymal marker genes in metastatic breast cancer patients casts light on the role of T-type VGCCs in metastasis and their involved in tumor invasiveness.

Keywords

• Breast cancer
• Metastasis
• EMT
• T-type VGCCs
• CACNA1H
• CACNA1I