The capability of GPCR agonists to positively regulate glycosylated receptor signaling in the absence of their ligands presents a role of cannabinoid receptors CB1 and CB2 signaling in activating numerous receptor tyrosine kinases and Toll-like receptors in the induction of altered epigenetic landscape(s) in cancer cells which might transmogrify cancer metabolism and epigenetic reprogramming to a metastatic phenotype. The gene discussed is CNR1; the disease is cancer.