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


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.

SUBMITTER: Shin SH 

PROVIDER: S-EPMC6173745 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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

Shin Seung-Hyun SH   Lee Ga Young GY   Lee Mingyu M   Kang Jengmin J   Shin Hyun-Woo HW   Chun Yang-Sook YS   Park Jong-Wan JW  

Nature communications 20181005 1


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-relat  ...[more]

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