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

Yuqing Wang, Wei Wang, Haoming Wu, Yu Zhou, Xiaodan Qin, Yan Wang, Jia Wu, Xiu-Yuan Sun, Yan Yang, Hui Xu, Xiaoping Qian, Xuewen Pang, Yan Li, Zhiqian Zhang, Jiahuai Han and Yu Zhang ()
Additional contact information
Yuqing Wang: Peking University. NHC Key Laboratory of Medical Immunology (Peking University)
Wei Wang: Peking University. NHC Key Laboratory of Medical Immunology (Peking University)
Haoming Wu: Peking University. NHC Key Laboratory of Medical Immunology (Peking University)
Yu Zhou: Peking University. NHC Key Laboratory of Medical Immunology (Peking University)
Xiaodan Qin: Peking University. NHC Key Laboratory of Medical Immunology (Peking University)
Yan Wang: Peking University. NHC Key Laboratory of Medical Immunology (Peking University)
Jia Wu: Peking University. NHC Key Laboratory of Medical Immunology (Peking University)
Xiu-Yuan Sun: Peking University. NHC Key Laboratory of Medical Immunology (Peking University)
Yan Yang: Jinzhou Medical University
Hui Xu: Jinzhou Medical University
Xiaoping Qian: Peking University. NHC Key Laboratory of Medical Immunology (Peking University)
Xuewen Pang: Peking University. NHC Key Laboratory of Medical Immunology (Peking University)
Yan Li: Peking University. NHC Key Laboratory of Medical Immunology (Peking University)
Zhiqian Zhang: Peking University Cancer Hospital and Institute
Jiahuai Han: Xiamen University
Yu Zhang: Peking University. NHC Key Laboratory of Medical Immunology (Peking University)

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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-1α 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.

Date: 2021
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DOI: 10.1038/s41467-021-21993-9

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