Aberrant expression of CITED2 promotes prostate cancer metastasis by activating the nucleolin-AKT pathway

Seung-Hyun Shin, Ga Young Lee, Mingyu Lee, Jengmin Kang, Hyun-Woo Shin, Yang-Sook Chun and Jong-Wan Park ()
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Seung-Hyun Shin: Seoul National University College of Medicine
Ga Young Lee: Seoul National University College of Medicine
Mingyu Lee: Seoul National University College of Medicine
Jengmin Kang: Seoul National University College of Medicine
Hyun-Woo Shin: Seoul National University College of Medicine
Yang-Sook Chun: Seoul National University College of Medicine
Jong-Wan Park: Seoul National University College of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06606-2

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