CXCR4 and nonpapillary renal cell carcinoma: In addition, since CXCR4 transduces a signal by increasing intracellular calcium ion levels and enhanced the activation of MAPK1/MAPK3 pathway [43,44], and activating the MAPK1/MAPK3 signaling pathway enhanced cancer progression in ovarian cancer [45], we conjectured that CXCR4 might activated the MAPK1/MAPK3 pathway to facilitate ccRCC development.