Targeting PRPK Function Blocks Colon Cancer Metastasis

Molecular Cancer Therapeutics
Tatyana ZykovaZigang Dong

Abstract

The biological functions of the p53-related protein kinase (PRPK) remain unclear. We have previously demonstrated that PRPK is phosphorylated by the T-LAK cell-originated protein kinase (TOPK) and that phosphorylated PRPK (p-PRPK) promotes colon cancer metastasis. Here, we analyzed colon adenocarcinomas from 87 patients and found that higher expression levels of p-PRPK were associated with later stages of metastatic dissemination (stage III and IV) as compared with earlier stages (stages I and II). Indeed, levels of p-PRPK were higher in metastatic versus malignant human colon adenocarcinomas. Knocking down PRPK expression attenuated colorectal liver and lung metastasis of colon cancer cells in vivo An in vitro kinase assay indicated that active PRPK does not phosphorylate p53 directly. We found that PRPK phosphorylates survivin, a regulator of colon cancer metastasis. PRPK phosphorylates survivin at Thr34, which is important for survivin stability. Taken together, our data strongly suggest that the PRPK signaling pathway promotes colon cancer metastasis by modulating survivin stability, and that PRPK could be a new prognostic marker for the survival of colon cancer patients. In addition, we identified an FDA-approved bacterios...Continue Reading

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Citations

Oct 26, 2018·Cell Death & Disease·Katharine J HerbertGeoff S Higgins
Mar 11, 2020·Journal of Cancer Research and Clinical Oncology·Yanhua SunGuiying Wang
Feb 7, 2021·Communications Biology·Jian LiZigang Dong
Apr 28, 2020·Neoplasia : an International Journal for Oncology Research·Dongdong ChenRobert W Schnepp

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