What is it about?
GPRC5A was discovered in our lab through differential display analysis in cells treated with the phorbol ester TPA. Two years later, Lotan’s group reported that retinoic acid also stimulates this gene. We have now found that vitamin D similarly induces its expression. Interestingly, inhibition of PKC completely blocks the signaling pathways of both vitamin D and retinoic acid. It is now essential to determine whether this effect extends to other genes regulated by these vitamins.
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Why is it important?
These findings may also help uncover the long-elusive mechanisms underlying the chemopreventive actions described decades ago by Anita Roberts and Michael Sporn. Moreover, they may contribute to understanding the dual roles of these vitamins in cancer treatment and prevention—especially given that both PKC and GPRC5A exhibit similar dual behavior. While this duality has not been demonstrated in the present study, the path is now open for future investigation.
Perspectives
GPRC5A has been found recently as the main receptor for galectin-3; it induces GPRC5A endocitosis. This may have important consequences in several diseases, including cancer, its chemoprevention and treatment. In this regard, GPRC5A modulates key signalling pathways including EGFR/STAT3, NF-κB, PI3K/Akt, cAMP/CREB, and Hippo/YAP1, influencing cell proliferation, inflammation, and tumorigenesis.
Dr Tomás A. Santa Coloma
Institute for Biomedical Research (BIOMED), CONICET, UCA
Read the Original
This page is a summary of: Vitamin D and Retinoic Acid Require Protein Kinase C Activity and Reactive Oxygen Species as Opposing Signals Regulating PEIG-1/GPRC5A Expression in Caco-2 and T84 Colon Carcinoma Cells, Biomolecules, May 2025, MDPI AG,
DOI: 10.3390/biom15050711.
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