Fyn 激活的 YANK2 通过 mTOR 非依赖性 p70S6K 激活途径促进神经胶质瘤的发生。

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

机构信息

Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

Department of Clinical Laboratory, Zhengzhou Eighth People's Hospital, Zhengzhou, Henan, China.

出版信息

Sci Rep. 2024 May 7;14(1):10507. doi: 10.1038/s41598-024-61157-5.

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.

神经胶质瘤，尤其是胶质母细胞瘤（GBM），是一种无法治愈的脑肿瘤。大多数靶向受体酪氨酸激酶（RTKs）的药物并没有给 GBM 患者带来益处。目前仍在探索神经胶质瘤生长的机制，以寻找更有效的治疗方法。在这里，我们报告丝氨酸/苏氨酸蛋白激酶 YANK2（又一个激酶 2）在神经胶质瘤组织中上调，并促进神经胶质瘤在体外和体内的生长和增殖。此外，我们证实癌基因 Fyn 通过磷酸化 YANK2 的 Y110 直接激活 YANK2，并且 Fyn 介导的 YANK2 在 Y110 位点的磷酸化通过增加其稳定性来促进神经胶质瘤的生长。最后，证明 YANK2 是 p70S6K 的一个新的上游激酶，并通过直接磷酸化 p70S6K 的 T389 促进神经胶质瘤的生长。总之，我们发现了一条新的 mTOR 非依赖性 p70S6K 激活途径，即 Fyn-YANK2-p70S6K，它促进神经胶质瘤的生长，而 YANK2 是一种潜在的癌基因，可作为神经胶质瘤的新治疗靶点。