Activation of GPR54 promotes cell cycle arrest and apoptosis of human tumor cells through a specific transcriptional program not shared by other Gq-coupled receptors.
Becker. Jérôme A J JA; Mirjolet. Jean-François JF; Bernard. Jérôme J; Burgeon. Emmanuel E; Simons. Marie-Jeanne MJ; Vassart. Gilbert G; Parmentier. Marc M; Libert. Frédérick F
Key Findings
- Activating GPR54 with kisspeptin-10 leads to cell‑cycle arrest and apoptosis in human tumor cells.
- The gene‑expression changes caused by GPR54 are distinct from those caused by the bradykinin B2 receptor, despite both being Gq‑coupled.
- Blocking PLC or PKC stops the transcriptional response, indicating these pathways are essential for the effect.
Practical Outcomes
- For most biohackers focused on longevity, metabolism, or performance, this research offers little direct guidance. It suggests kisspeptin‑10 might have anti‑cancer properties, but no dosage, safety, or protocol information is provided, so it isn’t ready for self‑experimentation.
Summary
The study shows that the peptide kisspeptin-10, when it binds to its receptor GPR54 on certain cancer cells, triggers a unique set of genes that stop the cells from dividing and cause them to die. This effect is different from what happens when a similar receptor (the bradykinin B2 receptor) is activated, even though both use the same type of internal signaling protein.
Abstract
GPR54 is a receptor for peptides derived from the metastasis suppressor gene KiSS-1. To investigate the intracellular mechanisms involved in the reduction of the metastatic potential of MDA-MB-435S cells expressing GPR54, a time course stimulation by kisspeptin-10 over a period of 25 h was performed using cDNA microarrays. Comparison with the bradykinin B(2) receptor revealed a distinct pattern of gene regulation despite a common coupling to the G(q/11) class of G-proteins. Inhibitors of PLC and PK-C abolished the transcriptional regulation of all tested genes, while an inhibitor of p42/44 affected a subset of genes controlled both by GPR54 and B(2). Among the genes specifically up-regulated by GPR54, we found several proapoptotic genes. Stimulation of GPR54 promoted apoptosis while no significant change was observed after B(2) receptor activation. Our results suggest that the metastasis suppressor properties of GPR54 are mediated in part by cell cycle arrest and induction of apoptosis in malignant cells.
Study Information
pubmed
2005
2005-01-21T00:00:00.000Z
10.1016/j.bbrc.2004.11.094