不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
抑制 ALK-TOPK 信号通路可促进 ALK 阳性 NSCLC 的细胞凋亡
英文原题：Inhibiting ALK-TOPK signaling pathway promotes cell apoptosis of ALK-positive NSCLC.
查看英文原题
Inhibiting ALK-TOPK signaling pathway promotes cell apoptosis of ALK-positive NSCLC.
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中文摘要
T-LAK细胞来源的蛋白激酶（TOPK）是肿瘤的潜在治疗靶点。然而，其在间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌（NSCLC）中的作用尚未见报道。在此，我们发现TOPK在ALK阳性NSCLC中高表达。此外，通过体外激酶实验筛选，鉴定出ALK是TOPK的另一个上游激酶。随后，体外和离体实验证明ALK在Y74位点磷酸化TOPK，并通过磷酸化蛋白质组学分析探索了ALK-TOPK下游通路。接着，我们证明抑制TOPK可增强肿瘤对alectinib（一种ALK抑制剂）的敏感性。alectinib与HI-032（一种TOPK抑制剂）联合使用在离体和体内均抑制了ALK阳性NSCLC细胞的生长并促进了凋亡。我们的发现揭示了ALK阳性NSCLC中一条新的ALK-TOPK信号通路。alectinib与HI-032的联合使用可能是一种有前景的治疗策略，可提高ALK阳性NSCLC对靶向治疗的敏感性。
展开英文摘要原文
T-LAK cell-oriented protein kinase (TOPK) is a potential therapeutic target in tumors.
However, its role in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) has not been reported.
Here, we found that TOPK was highly expressed in ALK-positive NSCLC.
Additionally, ALK was identified as another upstream kinase of TOPK by in vitro kinase assay screening. Then, it was proven that ALK phosphorylated TOPK at Y74 in vitro and ex vivo, and the pathways downstream of ALK-TOPK were explored by phosphoproteomic analysis. Subsequently, we demonstrated that inhibiting TOPK enhanced tumor sensitivity to alectinib (an ALK inhibitor). The combination of alectinib and HI-032 (a TOPK inhibitor) suppressed the growth and promoted the apoptosis of ALK-positive NSCLC cells ex vivo and in vivo.
Our findings reveal a novel ALK-TOPK signaling pathway in ALK-positive NSCLC. The combination of alectinib and HI-032 might be a promising therapeutic strategy for improving the sensitivity of ALK-positive NSCLC to targeted therapy.
论文信息
- 作者
- Xiao J、Zhang L、Yi H、Zou L、Mo J、Xue F、Zheng J、Huang Y
- 第一作者单位
- Cancer Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China. xjjuan2006@glmc.edu.cn.China
- 通讯作者单位
- Cancer Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China. fengzhu@glmc.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Cell death & disease2022 Sep 27
- 原文标识
- PubMed 36167821 · DOI 10.1038/s41419-022-05260-3
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