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HIF-1 activates the transcription of genes that control multiple steps in the metastatic process. Blue, red, yellow, and orange ovals denote bulk cancer cells, cancer stem cells, bone marrow-derived cells (mesenchymal stem cells, myeloid-derived suppressor cells and tumor associated macrophages), and extracellular vesicles (exosomes and microvesicles) respectively. Cancer stem cells give rise to both stem cells and non-stem cells and can initiate secondary (metastatic) tumors.
