SPP1 and neoplasm: Moreover, pathway analysis revealed that SPP1+APOE+ TAM were regulated by the HIF-1 signaling pathway (Supplementary Fig. 3C, 3D), inducing expression of VEGFA, LDHA, and ALDOA46,47, which not only promotes hypoxia (Fig. 4g) but is another approach to induce EMT in tumor cells48.