HSPA5 and cancer: 14, 15 Our previous study also showed that downregulation of HIF-1α by K5 is responsible for the decreased VEGF expression in endothelial cells and lung cancer cells.16 Furthermore, K5 has been shown to directly induce apoptosis and cause cell cycle arrest in proliferating endothelial cells and stressed tumour cells through cell surface voltage-dependent anion channel (VDAC)17, 18 or GRP78.19, 20 However, the receptors and the downstream signals by which K5 downregulates HIF-1α and GRP78 in cancer cells have remained unknown.