The activation of GPCR (CXCR1 and CXCR2) activated by IL-8 promotes the activation of a variety of downstream pathways, including but may not be limited to PLC-PKC, PI3K-AKT, Rho-GTPase family, FAK/Src of non-receptor tyrosine kinases and MAPK cascade signals (Fig. 1b), which ultimately affect the progression of cancer, angiogenesis, metastasis, and cancer stem cell activation [39]. The gene discussed is HSPG2; the disease is cancer.