This XIST-driven production of IL-6 from ALDH− bulk tumor cells preferentially binds to IL6R on ALDH+ CSCs to drive STAT3 activation and expression of key CSC factors (i.e., c-MYC, KLF4 and SOX9), promoting self-renewal of ALDH+ CSCs (Fig. 8A). Here, STAT3 is linked to neoplasm.