Targeting TTK Inhibits Tumorigenesis of T‐Cell Lymphoma Through Dephosphorylating p38α and Activating AMPK/mTOR Pathway

• DOI: 10.1002/advs.202413990
• Publication Date: 2025-01-21T17:18:47Z
• Authors: Bingyu Liu; Tiange Lu; Mengfei Ding; Xiaoli Zhou; Yujie Jiang; Juanjuan Shang; Wenyue Sun; Shunfeng Hu; Xin Wang; Xiangxiang Zhou
• Keywords: p38α; phosphorylation; threonine tyrosine kinase; Science; T‐cell lymphoma; Q; ubiquitination

Abstract T‐cell lymphoma (TCL) is a group of non‐Hodgkin's with high heterogeneity and unfavorable prognosis. Current standard treatments have demonstrated limited efficacy in improving the outcomes for TCL patients. Therefore, identification novel drug targets urgently needed to improve prognosis Through multi‐omics analysis, aberrant expression threonine tyrosine kinase (TTK) identified. High TTK closely associated poor Targeting through gene knockdown exerts anti‐tumor effects vitro vivo, including inhibiting cell proliferation, inducing G2/M phase arrest, enhancing DNA damage apoptosis. Mechanically, p38α identified as potential phosphorylation substrate phosphoproteomic quantification motif prediction. Furthermore, inhibition suppresses activation dephosphorylating it at Thr180/Tyr182, thereby promoting AMPK/mTOR pathway. In addition, targeting enhances autophagy cells p38α. CFI‐402257, specific inhibitor TTK, found exhibit exerted synergistic PI3K inhibitor, Duvelisib, TCL. The study shows that contributes development by regulating p38α‐mediated CFI‐402257 expected be promising strategy treatment.