The researchers first analyzed tissue samples from human oral cancer tumors and healthy tongues. They found that the ORAI1 gene, which contains instructions for creating the ORAI1 calcium channel, was heavily overexpressed in the tumors but not in healthy tissue.and found that activating the ORAI1 calcium channel caused a large influx of calcium into cancer cells.
"These findings demonstrate an important role for ORAI1 in oral cancer progression and pain, but what is the mechanism? We wondered if MMP1 could be the messenger relaying pain," said Lacruz. They combined the fluid with neurons from the trigeminal ganglia, a collection of nerves in the face that transmit pain in oral cancer. The fluid from cancer cells without the ORAI1 gene did not elicit a strong response from the neurons, but the MMP1-rich fluid from cells with ORAI1 evoked an increase in action potentials, the necessary signal for pain transmission.
The researchers also ran experiments with abnormal but non-cancerous cells. When they overexpressed the ORAI1 gene in these non-invasive cells, they became invasive, raising the possibility that ORAI1 could play a role in cells switching from non-cancerous to cancerous cells.Several FDA-approved drugs block the ORAI1 calcium channel, but they have not yet been tested in oral cancer.
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