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

作者：Yuqing Wang, Wei Wang, Haoming Wu, Yu Zhou, Xiaodan Qin, Yan Wang, Jia Wu, Xiuyuan Sun, Yan Yang, Hui Xu, Xiaoping Qian, Xuewen Pang, Yan Li, Zhiqian Zhang, Jiahuai Han, Yu Zhang · 发表于：Nature Communications · 年份：2021 · DOI：10.1038/s41467-021-21993-9 · 被引用次数：30 · 研究领域：Cancer, Hypoxia, and Metabolism、Ubiquitin and proteasome pathways、Metabolism, Diabetes, and Cancer

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.