Matches in SemOpenAlex for { <https://semopenalex.org/work/W2767684755> ?p ?o ?g. }
- W2767684755 endingPage "15" @default.
- W2767684755 startingPage "1" @default.
- W2767684755 abstract "Wnt/β-catenin or canonical Wnt signaling pathway regulates the self-renewal of cancer stem-like cells (CSCs) and is involved in tumor progression and chemotherapy resistance. Previously, we reported that this pathway is activated in a subset of osteosarcoma CSCs and that doxorubicin induced stemness properties in differentiated cells through Wnt/β-catenin activation. Here, we investigated whether pharmacological Wnt/β-catenin inhibition, using a tankyrase inhibitor (IWR-1), might constitute a strategy to target CSCs and improve chemotherapy efficacy in osteosarcoma. IWR-1 was specifically cytotoxic for osteosarcoma CSCs. IWR-1 impaired spheres' self-renewal capacity by compromising landmark steps of the canonical Wnt signaling, namely translocation of β-catenin to the nucleus and subsequent TCF/LEF activation and expression of Wnt/β-catenin downstream targets. IWR-1 also hampered the activity and expression of key stemness-related markers. In vitro, IWR-1 induced apoptosis of osteosarcoma spheres and combined with doxorubicin elicited synergistic cytotoxicity, reversing spheres' resistance to this drug. In vivo, IWR-1 co-administration with doxorubicin substantially decreased tumor progression, associated with specific down-regulation of TCF/LEF transcriptional activity, nuclear β-catenin and expression of the putative CSC marker Sox2. We suggest that targeting the Wnt/β-catenin pathway can eliminate CSCs populations in osteosarcoma. Combining conventional chemotherapy with Wnt/β-catenin inhibition may ameliorate therapeutic outcomes, by eradicating the aggressive osteosarcoma CSCs and reducing drug resistance." @default.
- W2767684755 created "2017-11-17" @default.
- W2767684755 creator A5005407396 @default.
- W2767684755 creator A5012567466 @default.
- W2767684755 creator A5046390152 @default.
- W2767684755 creator A5055716052 @default.
- W2767684755 creator A5083401778 @default.
- W2767684755 creator A5090338115 @default.
- W2767684755 date "2018-02-01" @default.
- W2767684755 modified "2023-10-18" @default.
- W2767684755 title "IWR-1, a tankyrase inhibitor, attenuates Wnt/β-catenin signaling in cancer stem-like cells and inhibits in vivo the growth of a subcutaneous human osteosarcoma xenograft" @default.
- W2767684755 cites W1558726597 @default.
- W2767684755 cites W191900123 @default.
- W2767684755 cites W1945630201 @default.
- W2767684755 cites W1951102280 @default.
- W2767684755 cites W1951644923 @default.
- W2767684755 cites W1968384480 @default.
- W2767684755 cites W1973493635 @default.
- W2767684755 cites W1974532695 @default.
- W2767684755 cites W1980895192 @default.
- W2767684755 cites W1982398983 @default.
- W2767684755 cites W1988658871 @default.
- W2767684755 cites W1994229067 @default.
- W2767684755 cites W1995940184 @default.
- W2767684755 cites W2006239354 @default.
- W2767684755 cites W2006604617 @default.
- W2767684755 cites W2006806983 @default.
- W2767684755 cites W2009847071 @default.
- W2767684755 cites W2018321310 @default.
- W2767684755 cites W2020458598 @default.
- W2767684755 cites W2024152221 @default.
- W2767684755 cites W2029600778 @default.
- W2767684755 cites W2032583877 @default.
- W2767684755 cites W2040731170 @default.
- W2767684755 cites W2042173734 @default.
- W2767684755 cites W2047220059 @default.
- W2767684755 cites W2053363358 @default.
- W2767684755 cites W2057257265 @default.
- W2767684755 cites W2063282481 @default.
- W2767684755 cites W2063655127 @default.
- W2767684755 cites W2066307520 @default.
- W2767684755 cites W2069750786 @default.
- W2767684755 cites W2070834113 @default.
- W2767684755 cites W2073759231 @default.
- W2767684755 cites W2087124418 @default.
- W2767684755 cites W2089426706 @default.
- W2767684755 cites W2098412103 @default.
- W2767684755 cites W2100791698 @default.
- W2767684755 cites W2101889783 @default.
- W2767684755 cites W2103562758 @default.
- W2767684755 cites W2106409672 @default.
- W2767684755 cites W2107587741 @default.
- W2767684755 cites W2109069210 @default.
- W2767684755 cites W2109169395 @default.
- W2767684755 cites W2111048208 @default.
- W2767684755 cites W2117015472 @default.
- W2767684755 cites W2118453722 @default.
- W2767684755 cites W2118680832 @default.
- W2767684755 cites W2119462927 @default.
- W2767684755 cites W2120316065 @default.
- W2767684755 cites W2123745849 @default.
- W2767684755 cites W2133591683 @default.
- W2767684755 cites W2134137083 @default.
- W2767684755 cites W2136499741 @default.
- W2767684755 cites W2146357510 @default.
- W2767684755 cites W2148394396 @default.
- W2767684755 cites W2148676055 @default.
- W2767684755 cites W2149583941 @default.
- W2767684755 cites W2150301699 @default.
- W2767684755 cites W2150346488 @default.
- W2767684755 cites W2151503957 @default.
- W2767684755 cites W2153720415 @default.
- W2767684755 cites W2155017336 @default.
- W2767684755 cites W2155507705 @default.
- W2767684755 cites W2160288586 @default.
- W2767684755 cites W2163341100 @default.
- W2767684755 cites W2165188131 @default.
- W2767684755 cites W2216993934 @default.
- W2767684755 cites W2292009157 @default.
- W2767684755 cites W2412945422 @default.
- W2767684755 cites W2414798983 @default.
- W2767684755 cites W2559991132 @default.
- W2767684755 cites W946020316 @default.
- W2767684755 cites W2035070138 @default.
- W2767684755 doi "https://doi.org/10.1016/j.canlet.2017.11.004" @default.
- W2767684755 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29126913" @default.
- W2767684755 hasPublicationYear "2018" @default.
- W2767684755 type Work @default.
- W2767684755 sameAs 2767684755 @default.
- W2767684755 citedByCount "66" @default.
- W2767684755 countsByYear W27676847552018 @default.
- W2767684755 countsByYear W27676847552019 @default.
- W2767684755 countsByYear W27676847552020 @default.
- W2767684755 countsByYear W27676847552021 @default.
- W2767684755 countsByYear W27676847552022 @default.
- W2767684755 countsByYear W27676847552023 @default.
- W2767684755 crossrefType "journal-article" @default.
- W2767684755 hasAuthorship W2767684755A5005407396 @default.