Figure 1.

The cancer stem cell microenvironment. The niche or tumor microenvironment is essential for maintenance of stemness, and this also applies to CSCs where cell–cell interactions within the niche are required to support the role of CSCs in cancer initiation and progression. The CSC microenvironment also contributes to CSCs' resistance to drugs and other cancer therapies, thereby, promoting cancer recurrence. The tumor tissue microenvironment is composed of a variety of cells, including tumor cells, cancer stem cells, inflammatory cells, and cancer-associated fibroblasts, along with blood vessels and extracellular matrix. In response to hypoxic stress and matrix, CSCs induce growth factors and cytokines including IL-6, CXCL8, and VEGF to regulate their growth via EGFR, NOTCH, WNT, and other signaling cascades. JAK, Janus kinases; STAT, signal transducer, and activator of transcription; VEGF, vascular endothelial growth factor; HGF, hepatocyte growth factor; mTOR, mammalian target of rapamycin; IL, Interleukin; CXCL, CXC-motif chemokine ligand.