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Wnt Signaling in Osteosarcoma

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Current Advances in Osteosarcoma

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 804))

Abstract

Osteosarcoma (OS) is the most common primary bone malignancy diagnosed in children and adolescents with a high propensity for local invasion and distant metastasis. Despite current multidisciplinary treatments, there has not been a drastic change in overall prognosis within the last two decades. With current treatments, 60–70 % of patients with localized disease survive. Given a propensity of Wnt signaling to control multiple cellular processes, including proliferation, cell fate determination, and differentiation, it is a critical pathway in OS disease progression. At the same time, this pathway is extremely complex with vast arrays of cross-talk. Even though decades of research have linked the role of Wnt to tumorigenesis, there are still outstanding areas that remain poorly understood and even controversial. The canonical Wnt pathway functions to regulate the levels of the transcriptional co-activator β-catenin, which ultimately controls key developmental gene expressions. Given the central role of this mediator, inhibition of Wnt/β-catenin signaling has been investigated as a potential strategy for cancer control. In OS, several secreted protein families modulate the Wnt/β-catenin signaling, including secreted Frizzled-related proteins (sFRPs), Wnt inhibitory protein (WIF), Dickkopf proteins (DKK-1,2,3), sclerostin, and small molecules. This chapter focuses on our current understanding of Wnt/β-catenin signaling in OS, based on recent in vitro and in vivo data. Wnt activates noncanonical signaling pathways as well that are independent of β-catenin which will be discussed. In addition, stem cells and their association with Wnt/β-catenin are important factors to consider. Ultimately, the multiple canonical and noncanonical Wnt/β-catenin agonists and antagonists need to be further explored for potential targeted therapies.

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Authors and Affiliations

  1. The Hyundai Cancer Institute, CHOC Children’s Hospital, Orange, CA, USA

    Carol H. Lin

  2. Department of Orthopaedic Surgery and Chao Family Comprehensive Cancer Center, University of California, 101 The City Drive South, Irvine, Orange, CA, 92868, USA

    Carol H. Lin, Tao Ji, Cheng-Fong Chen & Bang H. Hoang M.D.

  3. Musculoskeletal Tumor Center, People’s Hospital, Peking University, Beijing, People’s Republic of China

    Tao Ji

  4. Department of Orthopaedics, Therapeutical and Research Center of Musculoskeletal Tumor, Taipei Veterans General Hospital, Taipei, Taiwan

    Cheng-Fong Chen

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  1. Carol H. Lin
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  2. Tao Ji
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  3. Cheng-Fong Chen
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  4. Bang H. Hoang M.D.
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Correspondence to Bang H. Hoang M.D. .

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Editors and Affiliations

  1. Division of Pediatrics, Department of Cancer Biology, The Mary V. and John A. Reilly Distinguished Chair, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Eugenie S. Kleinerman, M.D.

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Lin, C.H., Ji, T., Chen, CF., Hoang, B.H. (2014). Wnt Signaling in Osteosarcoma. In: Kleinerman, M.D., E. (eds) Current Advances in Osteosarcoma. Advances in Experimental Medicine and Biology, vol 804. Springer, Cham. https://doi.org/10.1007/978-3-319-04843-7_2

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