Wnt5a induces and maintains prostate cancer cells dormancy in bone

DOI PDF 被引用文献3件
  • Dong Ren
    Department of Orthopedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 1
  • Yuhu Dai
    Department of Orthopedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 1
  • Qing Yang
    Department of Orthopedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 1
  • Xin Zhang
    Department of Experimental Research, State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, China 2
  • Wei Guo
    Department of Orthopedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 1
  • Liping Ye
    Department of Experimental Research, State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, China 2
  • Shuai Huang
    Department of Orthopedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 1
  • Xu Chen
    Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 5
  • Yingrong Lai
    Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 6
  • Hong Du
    Department of Pathology, the First People’s Hospital of Guangzhou City, Guangzhou, China 7
  • Chuyong Lin
    Department of Experimental Research, State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, China 2
  • Xinsheng Peng
    Department of Orthopedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 1
  • Libing Song
    Department of Experimental Research, State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, China 2

説明

<jats:p>In a substantial fraction of prostate cancer (PCa) patients, bone metastasis appears after years or even decades of latency. Canonical Wnt/β-catenin signaling has been proposed to be implicated in dormancy of cancer cells. However, how these tumor cells are kept dormant and recur under control of Wnt/β-catenin signaling derived from bone microenvironment remains unknown. Here, we report that Wnt5a from osteoblastic niche induces dormancy of PCa cells in a reversible manner in vitro and in vivo via inducing Siah E3 Ubiquitin Protein Ligase 2 (SIAH2) expression, which represses Wnt/β-catenin signaling. Furthermore, this effect of Wnt5a-induced dormancy of PCa cells depends on receptor tyrosine kinase-like orphan receptor 2 (ROR2), and a negative correlation of ROR2 expression with bone metastasis–free survival is observed in PCa patients. Therefore, these results demonstrate that Wnt5a/ROR2/SIAH2 signaling axis plays a crucial role in inducing and maintaining PCa cells dormancy in bone, suggesting a potential therapeutic utility of Wnt5a via inducing dormancy of PCa cells in bone.</jats:p>

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