Pharmacological characterisation of store‑operated calcium entry in medulloblastoma cell lines

Abstract

Store-operated Ca2+ entry (SOCE) is the primary pathway of Ca2+ entry into mammalian cells. Re-modelling of the SOCE pathway has been suggested as the driving mechanism for many tumour phenotypes, such as cancer cell proliferation, migration, and metastasis. Although SOCE has been studied in many cancer types, calcium signalling, especially the SOCE pathway, is largely unexplored in medulloblastoma (MB). MB is the most common malignant paediatric brain tumour, and previously, we reported that some key SOCE components are upregulated in MB. The present study aimed to functionally characterise SOCE in MB cells. Using RT-PCR, the expression of different SOCE-regulating genes was examined cells of different MB subgroups. Our data indicate that specific subgroups of MB cells differentially express SOCE genes. For example, one key regulatory gene, ORAI1, showed a higher expression in the invasive MB subgroups 3. This difference was also reflected by a higher SOCE in these cells compared to cells from MB subgroups associated with lower invasive potential. Overall, the results highlight that distinct MB subgroups rely on differential gene expression that affects their SOCE activity. Future studies will require a functional characterisation to delineate if altered SOCE is causal for the invasiveness of MB, which will be a critical to understand the potential of SOCE as a therapeutic target for the treatment of MB.