A genetic discovery now offers hope for the selective destruction of cancer cells, through the mechanism used by the human body to absorb vitamin D.
Vitamin D is not only an essential nutrient, but also the precursor of calcitriol, a hormone that is essential for health. Calcitriol, through the intestine, regulates the uptake of phosphorus and calcium needed by bones, as well as cell growth and the proper functioning of muscles, nerve cells and the immune system.
Now, researchers have shown for the first time in a study published in Frontiers in Endocrinology (“SDR42E1 modulates vitamin D absorption and cancer pathogenesis: insights from an in vitro model“) that a specific gene, called SDR42E1, is crucial for the uptake of vitamin D from the intestine and its further metabolism – a discovery with many potential applications in precision medicine, including cancer treatment.
“Here we show that blocking or inhibiting SDR42E1 can selectively stop the growth of cancer cells,” said Dr. George Nemer, professor and associate dean of Research at the College of Health and Life Sciences at Hamad Bin Khalifa University in Qatar and the study’s corresponding author.
Mistaken Copying
Nemer and his colleagues took into account previous research that had found a specific mutation in the SDR42E1 gene on chromosome 16 that is associated with vitamin D deficiency. The mutation caused the protein to be disrupted, rendering it inactive.
The researchers used CRISPR/Cas9 to edit a cell line called HCT116 from a colon cancer patient. By doing so, they converted the active form of SDR42E1 to an inactive one. In HCT116 cells, SDR42E1 expression is normally high, indicating that the protein is essential for their survival.
Killed cancer cells
Once the defective copy of SDR42E1 was introduced, the viability of the cancer cells plummeted by 53%.
In addition, at least 4,663 genes changed their expression levels, indicating that SDR42E1 is a critical molecular switch in many reactions essential for cell health.
Many of these genes are normally involved in cancer-related cell signaling and in the absorption and metabolism of cholesterol-like molecules – consistent with SDR42E1’s central role in calcitriol synthesis.
These results suggest that blocking the gene can selectively kill cancer cells, leaving neighboring cells unharmed.
Double-edged sword
“Our results open up new potential avenues in precision oncology, although clinical translation still requires significant validation and long-term development,” said Dr. Nagam Nafiz Hedi, a professor at the Middle East University in Amman, Jordan, and first author of the study.
But vitamin D deficiency in selected cells is not the only potential application.
These results show that SDR42E1 has two directions.
By artificially “boosting” SDR42E1 levels in local tissues through gene technology, there may also be beneficial effects, leveraging the known health effects of calcitriol.
“Because SDR42E1 is involved in vitamin D metabolism, we could also target it in any of the diseases where vitamin D plays a regulatory role,” said Nemer, citing as an example nutritional studies that have shown that the hormone can reduce the risk of cancer, kidney disease, and autoimmune and metabolic disorders.”
“However, such broader applications must be made with caution, as the long-term effects of SDR42E1 on vitamin D balance are not yet fully understood,” Hedi cautioned.
