HIF1A and cancer: In addition, hypoxic niches are enriched of cancer stem cells (CSCs) that are usually chemoresistant [176], because they have higher expression of ABC transporters [177, 178] and HIF-1α-mediated up-regulation of MMP9, C-X-C chemokine receptor type 4 (CXCR4), osteopontin, IL-8 and VEGF [179] that promote invasion and chemoresistance.