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Updated: Jan 6, 2026

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HSP90 regulates osteosarcoma cell apoptosis by targeting the p53/TCF-1-mediated transcriptional network

Jie Yang1, Yu-Hang Li1, Ming-Tang He2

  • 1Department of Bone and Joint Surgery, Institute of Orthopedic Diseases, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China.

Journal of Cellular Physiology
|October 10, 2019
PubMed

Insights

Heat shock protein 90 (HSP90) regulates T cell factor 1 (TCF-1) in osteosarcoma (OS). TCF-1 overexpression impacts apoptosis, suggesting TCF-1 and p53 status are key for HSP90 inhibition therapy efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • Osteosarcoma (OS) is a common pediatric bone cancer with frequently deregulated Wnt/β-catenin signaling.
  • Heat shock protein 90 (HSP90) influences OS via the AKT/GSK-3β/β-catenin pathway.
  • The role of T cell factors/lymphoid enhancer-binding factor (TCFs/LEF) family members in OS remains unclear.

Purpose of the Study:

  • To investigate the role of TCF-1 in osteosarcoma.
  • To elucidate the relationship between HSP90, TCF-1, and apoptosis in OS.
  • To determine factors influencing therapeutic efficacy of HSP90 inhibition in OS.

Main Methods:

  • Comparative analysis of TCF-1 expression in OS versus other bone tumors.
  • TCF-1 knockdown experiments to assess effects on cell cycle, DNA damage, and apoptosis.
  • Investigation of HSP90 regulation of TCF-1 expression via β-catenin-dependent and proteasomal degradation pathways.
  • Analysis of p53 and miR-34a involvement in HSP90-regulated TCF-1 expression and apoptosis.

Main Results:

  • TCF-1 is overexpressed in OS compared to other bone tumors.
  • TCF-1 knockdown induces cell cycle arrest, DNA damage, and apoptosis.
  • HSP90 and TCF-1 are coexpressed in OS; HSP90 regulates TCF-1 via β-catenin or proteasomal degradation.
  • TCF-1 overexpression partially inhibits HSP90 inhibition-induced apoptosis.
  • p53, not miR-34a, is crucial for HSP90-regulated TCF-1 expression and apoptosis.

Conclusions:

  • TCF-1 is a key player in osteosarcoma pathogenesis and response to HSP90 inhibition.
  • TCF-1 expression levels and p53 status are critical determinants for optimizing HSP90 inhibitor therapy in OS.
  • Targeting TCF-1 or considering p53 status may enhance therapeutic strategies for osteosarcoma.
Keywords:
HSP90TCF-1apoptosisosteosarcomap53

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