CASR and neoplasm: In 2014, Joeckel et al. demonstrated in renal cell carcinoma (RCC) cells that the CaSR mediated the promotion function of extracellular Ca2+ on tumor cell proliferation and bone metastasis via activation of the PI3K (phosphatidyl-inositol 3-kinase)/AKT pathway, the PLCγ-1 pathway, and the mitogen activated protein kinase (MAPK) cascades [64,65].