Aberrant activation of Wnt/β-catenin signaling drives proliferation of bone sarcoma cells

Changbao Chen; Meng Zhao; Aixian Tian; Xiaolin Zhang; Zhi Yao; Xinlong Ma

doi:10.18632/oncotarget.4100

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Research Papers:

Aberrant activation of Wnt/β-catenin signaling drives proliferation of bone sarcoma cells

Changbao Chen, Meng Zhao, Aixian Tian, Xiaolin Zhang, Zhi Yao and Xinlong Ma _

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Oncotarget. 2015; 6:17570-17583. https://doi.org/10.18632/oncotarget.4100

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Abstract

Changbao Chen1,*, Meng Zhao2,*, Aixian Tian3, Xiaolin Zhang1, Zhi Yao2 and Xinlong Ma1

1 Department of Spinal Surgery, Tianjin Hospital, Tianjin, P. R. China

2 Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, P. R. China

3 Department of Medical Laboratory, Tianjin Hospital, Tianjin, P. R. China

* These authors have contributed equally to this work

Correspondence to:

Xinlong Ma, email:

Zhi Yao, email:

Keywords: bone sarcomas; Wnt/β-catenin signaling; autocrine wnt activation; cell proliferation; therapeutic target

Received: October 09, 2014 Accepted: March 30, 2015 Published: May 11, 2015

Abstract

Bone sarcomas such as osteosarcoma and chondrosarcoma are frequently refractory to conventional chemotherapy and radiotherapy that exhibit poor prognosis. The Wnt signaling are evolutionarily conserved and implicated in cell proliferation and sarcomagenesis. However, the potential role of the Wnt signaling in bone sarcomas is still unclear. Here we demonstrate aberrant activation of Wnt/β-catenin signaling in bone sarcoma cells, involving an autocrine Wnt signaling loop with upregulation of specific Wnt ligands and receptors. Activation of Wnt/β-catenin signaling with Wnt3a or GSK-3β inhibitor drives the proliferation of bone sarcoma cells, whereas downregulation of activated Wnt signaling with dnTCF4 or siLEF1 suppresses bone sarcoma proliferation and induces cell cycle arrest. Taken together, our findings establish the evidence that aberrant activation of Wnt/β-catenin pathway involving an autocrine Wnt singaling drives the proliferation of bone sarcoma cells, and identify the autocrine activation of the Wnt/β-catenin signaling as a potential novel therapeutic target for bone sarcomas.

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Research Papers:

Aberrant activation of Wnt/β-catenin signaling drives proliferation of bone sarcoma cells

Abstract