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Updated: Feb 4, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Aberrant expression of CITED2 promotes prostate cancer metastasis by activating the nucleolin-AKT pathway
Seung-Hyun Shin1,2,3, Ga Young Lee1,2,3, Mingyu Lee1,2,3
1Department of Biomedical Science, BK21-plus Education Program, Seoul National University College of Medicine, Seoul, Korea.
Abstract:
Despite many efforts to develop hormone therapy and chemotherapy, no effective strategy to suppress prostate cancer metastasis has been established because the metastasis is not well understood. We here investigate a role of CBP/p300-interacting transactivator with E/D-rich carboxy-terminal domain-2 (CITED2) in prostate cancer metastasis. CITED2 is highly expressed in metastatic prostate cancer, and its expression is correlated with poor survival. The CITED2 gene is highly activated by ETS-related gene that is overexpressed due to chromosomal translocation. CITED2 acts as a molecular chaperone to guide PRMT5 and p300 to nucleolin, thereby activating nucleolin. Informatics and experimental data suggest that the CITED2-nucleolin axis is involved in prostate cancer metastasis. This axis stimulates cell migration through the epithelial-mesenchymal transition and promotes cancer metastasis in a xenograft mouse model. Our results suggest that CITED2 plays a metastasis-promoting role in prostate cancer and thus could be a target for preventing prostate cancer metastasis.
Insights
CBP/p300-interacting transactivator with E/D-rich carboxy-terminal domain-2 (CITED2) promotes prostate cancer metastasis by activating nucleolin. Targeting CITED2 may offer a new strategy to prevent cancer spread.
Area of Science:
- Oncology
- Molecular Biology
Background:
- Prostate cancer metastasis remains a significant challenge despite advancements in therapy.
- Understanding the molecular mechanisms driving metastasis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of CBP/p300-interacting transactivator with E/D-rich carboxy-terminal domain-2 (CITED2) in prostate cancer metastasis.
- To elucidate the molecular pathway through which CITED2 influences cancer progression.
Main Methods:
- Analysis of CITED2 expression in metastatic prostate cancer tissues.
- Investigating the interaction of CITED2 with PRMT5, p300, and nucleolin.
- Evaluating the effect of the CITED2-nucleolin axis on cell migration and epithelial-mesenchymal transition (EMT).
- Assessment of CITED2's role in a xenograft mouse model of prostate cancer metastasis.
Main Results:
- CITED2 is highly expressed in metastatic prostate cancer and correlates with poor survival.
- CITED2 activates nucleolin by acting as a molecular chaperone for PRMT5 and p300.
- The CITED2-nucleolin axis promotes prostate cancer cell migration via EMT.
- CITED2 enhances cancer metastasis in a preclinical mouse model.
Conclusions:
- CITED2 plays a critical role in promoting prostate cancer metastasis.
- The CITED2-nucleolin pathway is a key driver of cancer progression and spread.
- CITED2 represents a potential therapeutic target for inhibiting prostate cancer metastasis.
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