AKT1 and renal cell carcinoma: Hence, there are many molecular mechanisms involved in the relationship between renal cell carcinoma, the immune system and bone metastasis, including TGF-β, TGF-α/EGF-R signaling, insulin mRNA binding protein-3 (IMP3), cadherin-11, PTHrP, calcium/CaSR, AKT/integrin-α5 signaling, matriptase, MET and miRNAs (Figure 1).