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Dickkopf-1 (DKK1) drives growth and metastases in castration-resistant prostate cancer
Letizia Rinella1, Gloria Fiorentino1, Mara Compagno2
1Department of Medical Sciences, University of Turin, Turin, Italy.
Cancer Gene Therapy
|May 13, 2024
Summary
Dickkopf-1 (DKK1) promotes the growth and spread of metastatic castration-resistant prostate cancer (mCRPC). Inhibiting DKK1 significantly reduced tumor growth and metastasis in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) presents a significant clinical challenge with poor prognosis.
- Identifying molecular drivers of mCRPC progression is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of Dickkopf-1 (DKK1), a Wnt signaling modulator, in the growth and metastatic progression of mCRPC.
- To evaluate the therapeutic potential of targeting DKK1 in mCRPC.
Main Methods:
- DKK1 was silenced using siRNA and deleted using CRISPR/Cas9 in PC3 and DU145 mCRPC cell lines.
- In vitro assays assessed cell growth, migration, cell cycle, and gene expression.
- A xenograft mouse model was employed to evaluate tumor growth and lung metastasis formation.
Main Results:
- DKK1 silencing and deletion reduced mCRPC cell growth and migration in vitro.
- DKK1 knockout cells showed cell cycle arrest, altered tubulin, and modulated metastasis-associated genes, including E-cadherin re-expression and Cadherin-11 down-regulation.
- In vivo, DKK1 deletion suppressed tumor growth and lung metastasis in the xenograft model.
Conclusions:
- DKK1 plays a critical role in the growth and metastatic dissemination of mCRPC.
- Targeting DKK1 represents a promising therapeutic strategy for mCRPC.
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