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.
Nature communications. 2018 Oct 05*** epublish ***
Seung-Hyun Shin, Ga Young Lee, Mingyu Lee, Jengmin Kang, Hyun-Woo Shin, Yang-Sook Chun, Jong-Wan Park
Department of Biomedical Science, BK21-plus Education Program, Seoul National University College of Medicine, Seoul, Korea., Department of Biomedical Science, BK21-plus Education Program, Seoul National University College of Medicine, Seoul, Korea. .