文章：

阻断癌细胞表面TIP1的功能结构域可通过β-连环蛋白/Wnt信号通路上调Midkine

Blocking the functional domain of cancer cell surface TIP1 upregulates Midkine via the β-catenin/Wnt signaling pathway 

原文发布日期：2025-06-18 

英文摘要：

Drug resistance exhibited by cancer cells remains one of the primary reasons for the failure of therapeutic approaches to increase the survival of cancer patients. Marginal improvement in therapeutic efficacy with current treatment approaches for non-small cell lung cancer (NSCLC) mandates new treatment strategies. Tax interacting Protein-1 (TIP1) is a radiation-inducible molecular target involved in various cancer pathways. TIP1 expression correlates with poor survival in NSCLC patients. Antibody blocking the functional domain of TIP1 reduced cell proliferation and sensitized cancer cells to radiation. A ten-fold increase in Midkine (MDK) was observed in the proteomic analysis of cells treated with anti-TIP1 antibody. Wnt signaling activation led to MDK upregulation at the mRNA and protein levels following TIP1 blockade. Genetic silencing of β-catenin abrogated the induction of MDK following anti-TIP1 antibody treatment. Inhibiting TIP1 along with MDK showed a reduction in the colony-forming capability of the cells, indicating that MDK upregulation might be a strategy employed by cancer cells to combat the anti-proliferative capabilities of the anti-TIP1 antibody. Co-targeting cell surface TIP1 and MDK may be an effective therapeutic strategy for NSCLC patients. 

摘要翻译：

癌细胞表现出的耐药性仍然是导致癌症患者治疗方案无法提高生存率的主要原因之一。当前非小细胞肺癌（NSCLC）治疗手段的疗效改善有限，亟需新的治疗策略。Tax相互作用蛋白1（TIP1）是一种辐射诱导型分子靶点，参与多种癌症通路。TIP1的表达水平与非小细胞肺癌患者的不良预后相关。通过抗体阻断TIP1功能域可抑制细胞增殖并增强癌细胞对辐射的敏感性。经抗TIP1抗体处理的细胞蛋白质组学分析显示中期因子（MDK）表达量提升十倍。TIP1阻断后，Wnt信号通路的激活导致MDK在mRNA和蛋白水平上的上调。β-连环蛋白的基因沉默消除了抗TIP1抗体处理后对MDK的诱导作用。同时抑制TIP1和MDK可降低细胞集落形成能力，表明MDK上调可能是癌细胞对抗TIP1抗体增殖抑制能力的适应性策略。联合靶向细胞表面TIP1与MDK可能成为非小细胞肺癌患者的有效治疗策略。

原文链接：

Blocking the functional domain of cancer cell surface TIP1 upregulates Midkine via the β-catenin/Wnt signaling pathway