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Publication : The essential role of PRAK in tumor metastasis and its therapeutic potential.

First Author  Wang Y Year  2021
Journal  Nat Commun Volume  12
Issue  1 Pages  1736
PubMed ID  33741957 Mgi Jnum  J:303827
Mgi Id  MGI:6515232 Doi  10.1038/s41467-021-21993-9
Citation  Wang Y, et al. (2021) The essential role of PRAK in tumor metastasis and its therapeutic potential. Nat Commun 12(1):1736
abstractText  Metastasis is the leading cause of cancer-related death. Despite the recent advancements in cancer treatment, there is currently no approved therapy for metastasis. The present study reveals a potent and selective activity of PRAK in the regulation of tumor metastasis. While showing no apparent effect on the growth of primary breast cancers or subcutaneously inoculated tumor lines, Prak deficiency abrogates lung metastases in PyMT mice or mice receiving intravenous injection of tumor cells. Consistently, PRAK expression is closely associated with metastatic risk in human cancers. Further analysis indicates that loss of function of PRAK leads to a pronounced inhibition of HIF-1alpha protein synthesis, possibly due to reduced mTORC1 activities. Notably, pharmacological inactivation of PRAK with a clinically relevant inhibitor recapitulates the anti-metastatic effect of Prak depletion, highlighting the therapeutic potential of targeting PRAK in the control of metastasis.
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