Voltage-gated calcium channels: Novel targets for cancer therapy

Abstract

Voltage-gated calcium channels (VGCCs) comprise five subtypes: The L-type; R-type; N-type; P/Q-type; and T-type, which are encoded by α₁ subunit genes. Calcium ion channels also have confirmed roles in cellular functions, including mitogenesis, proliferation, differentiation, apoptosis and metastasis. An association between VGCCs, a reduction in proliferation and an increase in apoptosis in prostate cancer cells has also been reported. Therefore, in the present study, the online clinical database Oncomine was used to identify the alterations in the mRNA expression level of VGCCs in 19 cancer subtypes. Overall, VGCC family genes exhibited under-expression in numerous types of cancer, including brain, breast, kidney and lung cancers. Notably, the majority of VGCC family members (CACNA1C, CACNA1D, CACNA1A, CACNA1B, CACNA1E, CACNA1H and CACNA1I) exhibited low expression in brain tumors, with mRNA expression levels in the top 1-9% of downregulated gene rankings. A total of 5 VGCC family members (CACNA1A, CACNA1B, CACNA1E, CACNA1G and CACNA1I) were under-expressed in breast cancer, with a gene ranking in the top 1-10% of the low-expressed genes compared with normal tissue. In kidney and lung cancers, CACNA1S, CACNA1C, CACNA1D, CACNA1A and CACNA1H exhibited low expression, with gene rankings in the top 1-8% of downregulated genes. In conclusion, the present findings may contribute to the development of new cancer treatment approaches by identifying target genes involved in specific types of cancer.

Keywords: Oncomine; cancer; meta-analysis; potential biomarker; under-expression; voltage-gated calcium channels.

Figure 1.

Flow chart describing the process of data identification and accumulation for the quantitative analysis.

Figure 2.

Under-expression of 10 voltage-gated calcium channel genes in 19 types of cancers. The comparison of cancer vs. normal tissue was shown at different expression levels based on P<0.001, a fold change >2.0 and a gene rank percentile <10%, to screen the microarray datasets. The color alterations represent the changes in level of gene rank percentage.

Figure 3.

Plots showing voltage-gated calcium channel family gene mRNA expression z-scores vs. copy number value from 967 cell lines that were obtained through the Cancer Cell Line Encyclopedia. Each dot represents one cell line.