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

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.

• Authors: Changbao Chen, Meng Zhao, Aixian Tian, Xiaolin Zhang, Zhi Yao, Xinlong Ma
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 19 Pg. 17570-83 (Jul 10 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25999350 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CTNNB1 protein, human
• RNA, Small Interfering
• beta Catenin

Topics

• Blotting, Western
• Bone Neoplasms (metabolism, pathology)
• Cell Cycle Checkpoints (physiology)
• Cell Line, Tumor
• Cell Proliferation
• Humans
• RNA, Small Interfering
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Sarcoma (metabolism, pathology)
• Transfection
• Wnt Signaling Pathway (physiology)
• beta Catenin (metabolism)