INOS promotes CD24⁺CD133⁺ liver cancer stem cell phenotype through a TACE/ADAM17-dependent Notch signaling pathway.

ABSTRACT: The inducible nitric oxide synthase (iNOS) is associated with more aggressive solid tumors, including hepatocellular carcinoma (HCC). Notch signaling in cancer stem cells promotes cancer progression and requires Notch cleavage by ADAM (a disintegrin and metalloprotease) proteases. We hypothesized that iNOS/NO promotes Notch1 activation through TACE/ADAM17 activation in liver cancer stem cells (LCSCs), leading to a more aggressive cancer phenotype. Expression of the stem cell markers CD24 and CD133 in the tumors of patients with HCC was associated with greater iNOS expression and worse outcomes. The expression of iNOS in CD24⁺CD133⁺ LCSCs, but not CD24^-CD133^- LCSCs, promoted Notch1 signaling and stemness characteristics in vitro and in vivo, as we

SUBMITTER: Wang R 

PROVIDER: S-EPMC6205478 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature