NANOG and neoplasm: Conversely, knockdown of ALKBH5 impairs hypoxia-induced NANOG expression and BCSC enrichment, and also impairs tumor formation in vivo.73 Thus, HIF-induced ALKBH5 expression mediates the upregulation of pluripotency factor expression and the enrichment/specification of BCSCs in the hypoxic tumor microenvironment through negative modulation of RNA methylation (see Fig. 3b).