2. Academic Validation
  3. YANK2 activated by Fyn promotes glioma tumorigenesis via the mTOR-independent p70S6K activation pathway

YANK2 activated by Fyn promotes glioma tumorigenesis via the mTOR-independent p70S6K activation pathway

  • Sci Rep. 2024 May 7;14(1):10507. doi: 10.1038/s41598-024-61157-5.
Yue Shi 1,  Yue Cheng 1 2,  Wei Wang 1,  Liu Tang 1,  Wensheng Li 1,  Liyuan Zhang 1,  Zheng Yuan 1,  Feng Zhu 3 4,  Qiuhong Duan 5 6 7
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
  • 2 Department of Clinical Laboratory, Zhengzhou Eighth People's Hospital, Zhengzhou, Henan, China.
  • 3 Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, China. fengzhu@hust.edu.cn.
  • 4 Medical and Industry Crossover Research Institute of Medical College, Henan University, Kaifeng, 475000, Henan, China. fengzhu@hust.edu.cn.
  • 5 Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China. duanqhwz@hust.edu.cn.
  • 6 Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, China. duanqhwz@hust.edu.cn.
  • 7 Medical and Industry Crossover Research Institute of Medical College, Henan University, Kaifeng, 475000, Henan, China. duanqhwz@hust.edu.cn.
PMID: 38714727 DOI: 10.1038/s41598-024-61157-5
Abstract

Glioma, particularly glioblastomas (GBM), is incurable brain tumor. The most targeted receptor tyrosine kinase (RTKs) drugs did not bring benefit to GBM patients. The mechanism of glioma growth continues to be explored to find more effective treatment. Here, we reported that Ser/Thr protein kinase YANK2 (yet another kinase 2) is upregulated in glioma tissues and promotes the growth and proliferation of glioma in vitro and in vivo. Further, we confirmed that oncogene Fyn directly activated YANK2 through phosphorylation its Y110, and Fyn-mediated YANK2 phosphorylation at Y110 site promotes glioma growth by increasing its stability. Finally, YANK2 was proved to be a novel upstream kinase of p70S6K and promotes glioma growth by directly phosphorylating p70S6K at T389. Taken together, we found a new mTOR-independent p70S6K activation pathway, Fyn-YANK2-p70S6K, which promotes glioma growth, and YANK2 is a potential oncogene and serves as a novel therapeutic target for glioma.

Keywords

Fyn; Glioma; Tumorigenesis; YANK2; p70S6K.

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