淋巴细胞抗原6K (LY6K) 是一种小GPI连接的蛋白质，通常在睾丸中表达。LY6K的过度表达与多种实体癌症的不良生存结果显著相关，包括乳腺癌、卵巢癌、胃肠道癌、头颈部癌、脑癌、膀胱癌和肺癌。癌细胞的ERK-AKT和TGF-β通路需要LY6K，在体内肿瘤生长也需要LY6K。在本报告中，我们描述了LY6K在有丝分裂和细胞分裂中通过极性体激酶B和其底物组蛋白H3信号轴扮演的新角色。此外，我们还描述了小分子NSC243928与LY6K蛋白质的分子相互作用结构基础，以及由于LY6K-NSC243928相互作用导致LY6K-极性体激酶B信号在细胞周期中的破坏。总体而言，通过NSC243928干扰LY6K功能导致癌细胞的细胞分裂失败、多核细胞、DNA损伤、衰老和凋亡。LY6K对生命重要器官功能不是必需的，因此抑制LY6K信号传导是治疗难以治愈的癌症的理想方法，如三阴性乳腺癌。由Elsevier B.V.出版

Lymphocyte antigen 6K (LY6K) is a small GPI-linked protein that is normally expressed in testes. Increased expression of LY6K is significantly associated with poor survival outcomes in many solid cancers, including cancers of the breast, ovary, gastrointestinal tract, head and neck, brain, bladder, and lung. LY6K is required for ERK-AKT and TGF-β pathways in cancer cells and is required for in vivo tumor growth. In this report, we describe a novel role for LY6K in mitosis and cytokinesis through aurora B kinase and its substrate histone H3 signaling axis. Further, we describe the structural basis of the molecular interaction of small molecule NSC243928 with LY6K protein and the disruption of LY6K-aurora B signaling in cell cycle progression due to LY6K-NSC243928 interaction. Overall, disruption of LY6K function via NSC243928 led to failed cytokinesis, multinucleated cells, DNA damage, senescence, and apoptosis of cancer cells. LY6K is not required for vital organ function, thus inhibition of LY6K signaling is an ideal therapeutic approach for hard-to-treat cancers that lack targeted therapy such as triple-negative breast cancer.Published by Elsevier B.V.