Targeting the Wnt/β-catenin pathway in human osteosarcoma cells

Fang Fang, Ashley VanCleave, Ralph Helmuth, Haydee Torres, Kirby Rickel, Hannah Wollenzien, Hongli Sun, Erliang Zeng, Jing Zhao, Jianning Tao

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Aberrant activation of Wnt signaling has been implicated in human osteosarcoma, which may provide a genetic vulnerability that can be targeted in osteosarcoma treatment. To test whether Wnt activation is necessary for osteosarcoma growth, colony formation, invasion, and metastasis, we treated human osteosarcoma cells with a small molecule inhibitor of Wnt/β-catenin, PRI-724, which suppresses Wnt/β-catenin-mediated transcription. We found increased protein levels of endogenous active-β-catenin in five human osteosarcoma cell lines. Treatment with PRI-724 was sufficient to inhibit human osteosarcoma 143B and SJSA-1 cell proliferation. Suppressed Wnt signaling was confirmed by decreased protein levels of the Wnt target Cyclin D1. Furthermore, we revealed significant inhibitory effects on cell migration, invasion, and colony formation in the human osteosarcoma cells. Using deposited data from next generation sequencing studies, we analyzed somatic mutations and gene expression of components in the Wnt/β-catenin pathway. We found somatic mutations and upregulated gene expression of many components in the Wnt/ β-catenin pathway, indicating activated Wnt signaling. Taken together, our results illustrate the critical role of Wnt/β-catenin signaling in human osteosarcoma pathogenesis and growth, as well as the therapeutic potential of Wnt inhibitors in the treatment of human osteosarcoma.

Original languageEnglish (US)
Pages (from-to)36780-36792
Number of pages13
JournalOncotarget
Volume9
Issue number95
StatePublished - Dec 1 2018

Keywords

  • Cyclin D1
  • Osteosarcoma
  • PRI-724
  • Wnt/β-catenin signaling

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Fang, F., VanCleave, A., Helmuth, R., Torres, H., Rickel, K., Wollenzien, H., Sun, H., Zeng, E., Zhao, J., & Tao, J. (2018). Targeting the Wnt/β-catenin pathway in human osteosarcoma cells. Oncotarget, 9(95), 36780-36792.