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Updated: Feb 26, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
The TGF-β signalling negative regulator PICK1 represses prostate cancer metastasis to bone
Yuhu Dai1,2, Dong Ren1,2, Qing Yang1,2
1Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58# Zhongshan 2rd Road, Guangzhou 510080, China.
Abstract:
Backgroud:Constitutive activation of TGF-β signalling is a well-recognised mechanism in bone metastasis of prostate cancer (PCa). Protein Interacting with PRKCA 1 (PICK1) is a critical negative regulator of the TGF-β pathway. However, the clinical significance and biological role of PICK1 in PCa bone metastasis remain obscure.
Methods:
PICK1 expression is evaluated by immunohistochemistry (IHC) in 198 PCa patients. Statistical analysis is performed to explore correlation between PICK1 expression and clinicopathological features in PCa patients. The biological role of PICK1 is examined in PC-3 and C4-2B cells in vitro and a mouse intracardial model in vivo.
Results:
PICK1 expression is decreased in PCa tissues with bone metastasis and bone-derived cells and downregulation of PICK1 positively correlates with serum PSA level, Gleason grade and bone metastasis status in PCa patients. Overexpression of PICK1 suppresses PCa cell invasion and migration in vitro and bone metastasis in vivo. Our results further indicate downregulation of PICK1 is caused by miR-210-3p overexpression in PCa tissues with bone metastasis. Clinical negative correlation of PICK1 with miR-210-3p is confirmed in PCa tissues.
Conclusions:
Our findings uncover a novel functionally and clinically relevant epigenetic regulatory mechanism for constitutive activation of TGF-β signalling in bone metastasis of PCa.
Insights
Decreased PICK1 expression in prostate cancer (PCa) correlates with bone metastasis. Upregulating PICK1 inhibits PCa bone metastasis, revealing a new epigenetic mechanism involving miR-210-3p.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis
Background:
- Constitutive activation of TGF-β signaling drives prostate cancer (PCa) bone metastasis.
- Protein Interacting with PRKCA 1 (PICK1) acts as a negative regulator of the TGF-β pathway.
- The role of PICK1 in PCa bone metastasis is not well understood.
Purpose of the Study:
- To investigate the clinical significance of PICK1 in PCa bone metastasis.
- To elucidate the biological role of PICK1 in PCa progression.
- To identify regulatory mechanisms of PICK1 in PCa bone metastasis.
Main Methods:
- Immunohistochemistry (IHC) to assess PICK1 expression in 198 PCa patients.
- Statistical analysis correlating PICK1 with clinicopathological features.
- In vitro (PC-3, C4-2B cells) and in vivo (mouse intracardial model) experiments to study PICK1 function.
Main Results:
- Reduced PICK1 expression in metastatic PCa tissues and bone-derived cells.
- Downregulation of PICK1 correlates with higher PSA, Gleason grade, and bone metastasis.
- PICK1 overexpression suppresses PCa cell invasion, migration, and bone metastasis.
- miR-210-3p overexpression causes PICK1 downregulation in metastatic PCa.
- Inverse correlation between PICK1 and miR-210-3p in PCa tissues.
Conclusions:
- PICK1 downregulation, driven by miR-210-3p, is a key mechanism in PCa bone metastasis.
- This uncovers a novel epigenetic regulatory pathway for TGF-β signaling in PCa bone metastasis.
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