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

doi:10.18632/oncotarget.26377

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

Journal article

Open access

Peer reviewed

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 and Jianning Tao

Oncotarget, Vol.9(95), pp.36780-36792

12/01/2018

DOI: 10.18632/oncotarget.26377

PMCID: PMC6298399

PMID: 30613366

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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.

β-catenin signaling

Research Paper

PRI-724

Wnt

Cyclin D1

osteosarcoma

Details

Title: Subtitle: Targeting the Wnt/β-catenin pathway in human osteosarcoma cells
Creators: Fang Fang - Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
Ashley VanCleave - Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
Ralph Helmuth - Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
Haydee Torres - Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
Kirby Rickel - Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
Hannah Wollenzien - Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
Hongli Sun - Department of Oral and Maxillofacial Surgery, University of Iowa, Iowa City, IA, USA
Erliang Zeng - Departments of Preventive & Community Dentistry, Biomedical Engineering, and Biostatistics, Division of Biostatistics and Computational Biology of College of Dentistry, University of Iowa, Iowa City, IA, USA
Jing Zhao - Population Health Group, Sanford Research, Sioux Falls, SD, USA
Jianning Tao - Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA
Resource Type: Journal article
Publication Details: Oncotarget, Vol.9(95), pp.36780-36792
DOI: 10.18632/oncotarget.26377
PMID: 30613366
PMCID: PMC6298399
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Publisher: Impact Journals LLC
Language: English
Date published: 12/01/2018
Academic Unit: Preventive and Community Dentistry; Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute; Biostatistics; Craniofacial Anomalies Research Center; Oral and Maxillofacial Surgery; Dental Research
Record Identifier: 9984071938302771

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