Cancer upregulated gene 2 (CUG2), a novel oncogene, promotes stemness-like properties via the NPM1-TGF-β signaling axis
2019
Abstract Our previous study reported that cancer upregulated gene (CUG)2, a novel oncogene, induces both faster cell migration and anti-cancer drug resistance. We thus wonder whether CUG2 also induces
stemness, a characteristic of cancer
stemcells (CSCs) and further examine the molecular mechanism of this
phenotype. To test that CUG2 induces
stemness, we examined expression of
stemness-related factors. Overexpression of CUG2 enhanced expression levels of
stemness-related factors in human lung carcinoma A549 and immortalized bronchial BEAS-2B cells. Consequently, CUG2 increased cellular spherical cluster forming ability. Overexpression of CUG2 also induced tumor formation in xenotransplanted nude mice whereas transplantation of control cells failed to, implying that CUG2 possesses malignant tumorigenic potential. We paid attention to
nucleophosmin(
NPM1) for its known interaction with CUG2. Suppression of
NPM1hindered the CUG2-mediated
stemness-like
phenotypesand diminished TGF-β transcriptional activity and signaling. TGF-β increased
stemness-like
phenotypesin the control cells whereas TGF-β inhibitor blocked induction of the
phenotypes, indicating that
NPM1is required for CUG2-mediated
stemness-like
phenotypesthrough TGF-β signaling. Furthermore, the suppression of
Smad- and non-
Smad-dependent TGF-β signaling pathways also prevented CUG2 from inducing
stemness-like
phenotypes. Altogether, we suggest that the novel CUG2 oncogene promotes cellular transformation and
stemness, mediated by nuclear
NPM1protein and TGF-β signaling.
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