Fig. 2
Cell type-dependent impact of hypoxic conditions on CD133 expression. a Under hypoxic conditions and in certain types of cancer as indicated, HIF-1α and HIF-1β are translocated into the nucleus, where they form a heterodimeric transcription factor that binds to hypoxia-responsive elements (HRE), resulting in increased expression of CD133 and other stemness markers (e.g., KLF4 and SOX2). Thus, hypoxia can promote chemoresistance, invasiveness and EMT. b In gastrointestinal carcinoma cells, the induction of hypoxia either by lowering the partial pressure of oxygen or by applying hypoxia-mimicking agents such as DFO and CoCl2 downregulates CD133 expression (black dashed arrow). Reciprocally, rapamycin-mediated inhibition of mammalian TOR (red dashed arrow), an upstream regulator of HIF-1α signaling, results in the downregulation of HIF-1α and elevated levels of CD133 (red arrow). Illustrations in panels a and b are based on data presented in Refs [130] and [139], respectively, among others