biostudies-literatureWan XNatural Science Foundation of Hunan ProvinceInnovation-Driven Project of Central South UniversityNational Natural Science Foundation of ChinaHunan Provincial Natural Science Foundatione2412985https://www.ebi.ac.uk/biostudies/studies/S-EPMC11984844biostudies-literatureUnknown12(14)Eukaryotic elongation factor 2 kinase (eEF2K) has been considered as a putative target for cancer therapy; however, the underlying mechanisms of eEF2K in triple-negative breast cancer (TNBC) progression remain to be fully elucidated. In this study, it is shown that eEF2K is highly expressed in TNBC and is associated with poor prognosis. In vitro, in vivo, and patient-derived organoid experiments demonstrate that knockdown of eEF2K significantly impedes progression of TNBC. Proteomic analysis and confirmation experiments reveal that eEF2K positively regulates the mRNA and protein expressions of sex-determining region Y-box 8 (SOX8). Mechanistically, eEF2K binds to and phosphorylates aurora kinase A (AURKA) at S391, a newly identified phosphorylation site critical for maintaining AURKA proteAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Identification of a Novel Substrate for eEF2K and the AURKA-SOX8 as the Related Pathway in TNBC.PMC11984844819724808237306410533202217752247709322177086Yang JGong RZhong CJiang SWan XHe LYi WCheng YZhao XLi YYe NChen ZCao STian SZhu RShan TfalseIdentification of a Novel Substrate for eEF2K and the AURKA-SOX8 as the Related Pathway in TNBC.Eukaryotic elongation factor 2 kinase (eEF2K) has been considered as a putative target for cancer therapy; however, the underlying mechanisms of eEF2K in triple-negative breast cancer (TNBC) progression remain to be fully elucidated. In this study, it is shown that eEF2K is highly expressed in TNBC and is associated with poor prognosis. In vitro, in vivo, and patient-derived organoid experiments demonstrate that knockdown of eEF2K significantly impedes progression of TNBC. Proteomic analysis and confirmation experiments reveal that eEF2K positively regulates the mRNA and protein expressions of sex-determining region Y-box 8 (SOX8). Mechanistically, eEF2K binds to and phosphorylates aurora kinase A (AURKA) at S391, a newly identified phosphorylation site critical for maintaining AURKA prote2025-01-01T00:00:00Z2025 Apr2026-06-01T17:57:18.817Z2025-07-14T03:02:46.184ZS-EPMC119848443995079810.1002/advs.202412985