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Although many genes, such as p53 and Rb1, have been shown to be mutated, deregulation of the canonical Wnt\/\u03b2\u2010catenin signaling pathway is frequently observed in OS. We recently demonstrated that heat shock protein 90 (HSP90) is involved in the regulation of runt\u2010related transcription factor 2 via the AKT\/GSK\u20103\u03b2\/\u03b2\u2010catenin signaling pathway in OS. However, the precise role of T cell factors\/lymphoid enhancer\u2010binding factor (TCFs\/LEF) family members, which are the major binding complex of \u03b2\u2010catenin, in OS is poorly understood. In the present study, we first demonstrated that TCF\u20101 is overexpressed in OS compared with other bone tumors. Knockdown of TCF\u20101 significantly induced cell cycle arrest, severe DNA damage, and subsequent caspase\u20103\u2010dependent apoptosis. Interestingly, coexpression of HSP90 and TCF\u20101 was observed in OS, and mechanistically, we demonstrated that TCF\u20101 expression is regulated by HSP90 either through a \u03b2\u2010catenin\u2010dependent mechanism or a direct degradation of the proteasome. We also found that overexpression of TCF\u20101 partially abolishes the apoptosis induced by HSP90 inhibition. Furthermore, we provided evidence that p53, but not miR\u201034a, plays a crucial role in the HSP90\u2010regulated TCF\u20101 expression and subsequent apoptosis. Given the diverse combination regimens of HSP90 inhibition with some other treatments, we propose that the p53 status and the expression level of TCF\u20101 should be taken into consideration to enhance the therapeutic efficacy of HSP90 inhibition.<\/jats:p>","DOI":"10.1002\/jcp.29283","type":"journal-article","created":{"date-parts":[[2019,10,9]],"date-time":"2019-10-09T07:57:05Z","timestamp":1570607825000},"page":"3894-3904","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["HSP90 regulates osteosarcoma cell apoptosis by targeting the p53\/TCF\u20101\u2010mediated transcriptional network"],"prefix":"10.1002","volume":"235","author":[{"given":"Jie","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Bone and Joint Surgery, Institute of Orthopedic Diseases, The First Affiliated Hospital Jinan University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Hang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Bone and Joint Surgery, Institute of Orthopedic Diseases, The First Affiliated Hospital Jinan University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Tang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Longgang Orthopedics Hospital of Shenzhen  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju\u2010Feng","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Chashan Hospital of Dongguan  Dongguan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The Third Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lek Hang","family":"Cheang","sequence":"additional","affiliation":[{"name":"Department of Orthotraumaology Centro Hospitalar Conde S. 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