SPP1 and cancer: Other studies have reported the presence of different OPN isoforms in tumor cells in vivo where its presence correlates with tumor aggression, poor prognosis, and enhanced metastasis, at least in part by regulating PI3K/Akt/GSK3β and endothelial-mesenchymal transition (EMT) pathways, perhaps in some cancers through interaction with hypoxia-inducible factors (HIF-1α and 2α) (Gomaa et al., 2013; Jia et al., 2016).