HSPA5 and osteosarcoma: Similarly, hyperthermia upregulates GRP78 and GRP94 gene expression in human osteosarcoma cells and is associated with changes in cell membrane calcium levels and increases in calpain expression and activity [68], whereas transcriptional upregulation of GRP78 in GCs during goat follicular atresia suggests that it is more likely to be a major pathway regulating ER stress [69].