Identification of XD23 as a potent inhibitor of osteosarcoma via downregulation of DKK1 and activation of the WNT/β-catenin pathway

Osteosarcoma, the most prevalent malignant bone tumor, is notorious for its aggressive growth and invasiveness. The highly mutable genome of osteosarcoma has made identifying a key oncogene challenging, hindering the development of targeted treatments. Our study validates the effectiveness of XD23, an anti-cancer agent we previously identified, in curbing osteosarcoma proliferation, metastasis, EMT differentiation, and bone destruction and promoting osteosarcoma apoptosis. It further elucidated that XD23 thwarts osteosarcoma by suppressing DKK1 expression, which in turn activates the WNT-β/Catenin pathway. This research presents the concrete evidence of DKK1's involvement in osteosarcoma development, offering a foundation for the development of DKK1 inhibitors as novel treatments for this disease.

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Publication Details

Journal
iScience
Published
2024-08-23
DOI
https://doi.org/10.1016/j.isci.2024.110758
Citations
2
Primary Topic
Cancer-related gene regulation
Type
article
Field-Weighted Citation Impact
0.47

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article

Identification of XD23 as a potent inhibitor of osteosarcoma via downregulation of DKK1 and activation of the WNT/β-catenin pathway

Qian Xie, Jianhui Liang, Huiren Tao, Yanni Shen et al.
2 citations
iScience
Cancer-related gene regulation
0.47
article

Identification of XD23 as a potent inhibitor of osteosarcoma via downregulation of DKK1 and activation of the WNT/β-catenin pathway

Qian Xie, Jianhui Liang, Huiren Tao, Yanni Shen, Chun Hu, Yan Wang, Yipei Yang, Tailin Wu
article en
2 citations

Abstract

Osteosarcoma, the most prevalent malignant bone tumor, is notorious for its aggressive growth and invasiveness. The highly mutable genome of osteosarcoma has made identifying a key oncogene challenging, hindering the development of targeted treatments. Our study validates the effectiveness of XD23, an anti-cancer agent we previously identified, in curbing osteosarcoma proliferation, metastasis, EMT differentiation, and bone destruction and promoting osteosarcoma apoptosis. It further elucidated that XD23 thwarts osteosarcoma by suppressing DKK1 expression, which in turn activates the WNT-β/Catenin pathway. This research presents the concrete evidence of DKK1's involvement in osteosarcoma development, offering a foundation for the development of DKK1 inhibitors as novel treatments for this disease.

iScienceVol. 27(9)
Shenyang Pharmaceutical University (CN), Shenzhen University (CN), Chinese Academy of Sciences (CN), University of Hong Kong - Shenzhen Hospital (CN), Shenzhen Institutes of Advanced Technology (CN), University of Hong Kong (HK)
National Natural Science Foundation of China
Openalex Percentile: Top 36%
Cancer-related gene regulation
0.47
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Identification of XD23 as a potent inhibitor of osteosarcoma via downregulation of DKK1 and activation of the WNT/β-catenin pathway — Qian Xie, Jianhui Liang, et al. · iScience (2024) | TGRS Research Map | TGRS