Aberrant expression of CITED2 promotes prostate cancer metastasis by activating the nucleolin-AKT pathway. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Shin, Seung-Hyun; Lee, Ga; Lee, Mingyu; Kang, Jengmin; Shin, Hyun-Woo; Chun, Yang-Sook; Park, Jong-Wan
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 14
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-06606-2
• Languages: English
• ISSNs: 2041-1723

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. TheCITED2 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. More effective strategies are needed to prevent prostate cancer metastasis. Here they report CBP/p300-interacting transactivator with E/D-rich carboxy-terminal domain-2 (CITED2) to interact with nucleolin, p300, and PRMT5 subunits, and reveal a role of CITED2-nucleolin axis in prostate cancer metastasis.