A New Potential Target for Treating Prostate Cancer Metastasis

Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related death among males, with more than one million diagnosed cases and 350.000 deaths just in 2018. Few days ago, researchers of the National University College of Medicine in Seoul (Korea) published on Nature Communications that CITED2, a transcriptional coregulator of p300/CBP, is uniquely overexpressed in prostate cancer cells, in which it promotes cell migration and metastasis. The authors showed that CITED2 is a target of ERG protein and its over-expression is highly associated to TMPRSS2-ERG gene fusion, which approximatively account for 30% of prostate cancers. 

In regard to the mechanism of action, CITED2 binds in the nucleus to nucleolin (NCL), an RNA-binding protein, inducing its cytoplasmic export. Once in the cytoplasm, the CITED2-NCL complex enhances the translation of AKT oncogene, which in turns increases cell migration and metastasis. The metastasis-promoting effect of CITED2 is abolished by CITED2 or NCL knockdown, as well as CITED2-dependent cell migration is almost completely attenuated by pharmacological inhibition of AKT. The identification of this molecular mechanism for metastatization in prostate cancer could bring new opportunities for the development of new prostate cancer treatments. ​

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Link to the journal

​References:
Global Cancer Observatory, International Agency for Research on Cancer, WHO (http://gco.iarc.fr/)

Seung-Hyun Shin, Ga Young, Mingyu Lee, Jengmin Kang, Hyun-Woo Shin, Yang-Sook Chun & Jong-Wan Park. Aberrant expression of CITED2 promotes prostate cancer metastasis by activating the nucleolin-AKT pathway. Nature Communicationsvolume 9, Article number: 4113 (2018)