Hypoxia also directly affects migration and invasion of the metastatic tumor cells through induction of hypoxia-inducible factor (HIF)-1α, which is under the control of several factors in osteosarcoma cells including TGF-β1 [157,158], miRNA-20b [159] and miRNA-33b [160]. Here, TGFB1 is linked to osteosarcoma.