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DBC1/CCAR2 is involved in the stabilization of androgen receptor and the progression of osteosarcoma

Sajeev Wagle1, See-Hyoung Park2, Kyoung Min Kim3

  • 1Department of Orthopedic Surgery, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.

Scientific Reports
|August 8, 2015
PubMed

Insights

Deleted in breast cancer 1 (DBC1) protein and androgen receptor (AR) are linked to osteosarcoma progression. Targeting DBC1-AR pathways may offer new therapeutic strategies for this bone cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Deleted in breast cancer 1 (DBC1/CCAR2) is implicated in tumorigenesis and acts as an androgen receptor (AR) co-activator.
  • Limited research exists on DBC1's role in osteosarcoma development and progression.

Purpose of the Study:

  • To investigate the role of DBC1 and AR in osteosarcoma.
  • To explore the relationship between DBC1 and AR in osteosarcoma progression.

Main Methods:

  • Immunohistochemistry was used to assess DBC1 and AR expression in osteosarcoma tissues.
  • siRNA-mediated knockdown of DBC1 and AR was performed in osteosarcoma cell lines (U2OS, SaOS2).
  • Cellular proliferation, invasion, and signaling pathways were analyzed. AR protein stabilization and ubiquitination were examined.

Main Results:

  • DBC1 and AR expression correlated with advanced clinical stage, higher histologic grade, and poorer patient survival.
  • DBC1 was identified as an independent prognostic indicator for overall and relapse-free survival.
  • Knockdown of DBC1 or AR significantly reduced osteosarcoma cell proliferation and invasion, inhibiting related signaling pathways.
  • DBC1 was found to stabilize AR protein by affecting its ubiquitination and proteasomal degradation.

Conclusions:

  • The DBC1-AR pathway plays a significant role in osteosarcoma progression.
  • DBC1's involvement in AR protein stabilization suggests it as a potential therapeutic target in osteosarcoma.

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