dGLYAT调节Gadd45介导的JNK激活和细胞侵袭。
dGLYAT modulates Gadd45-mediated JNK activation and cell invasion.
作者信息
Xu Meng, Ren Pu, Tian Juhui, Xiao Lisha, Hu Ping, Chen Ping, Li Wenzhe, Xue Lei
机构信息
The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai, China.
Zhuhai Precision Medical Center, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, Guangdong, China.
出版信息
Cell Div. 2022 Aug 6;17(1):4. doi: 10.1186/s13008-022-00080-5.
BACKGROUND
Cell invasion is a crucial step of tumor metastasis, finding new regulators of which offers potential drug targets for cancer therapy. Aberrant GLYAT expression is associated with human cancers, yet its role in cancer remains unknown. This study aims to understand the function and mechanism of Drosophila GLYAT in cell invasion.
RESULTS
We found that dGLYAT regulates Gadd45-mediated JNK pathway activation and cell invasion. Firstly, loss of dGLYAT suppressed scrib depletion- or Egr overexpression-induced JNK pathway activation and invasive cell migration. Secondary, mRNA-seq analysis identified Gadd45 as a potential transcriptional target of dGLYAT, as depletion of dGLYAT decreased Gadd45 mRNA level. Finally, Gadd45 knockdown suppressed scrib depletion-induced JNK pathway activation and cell invasion.
CONCLUSIONS
These evidences reveal the role of dGLYAT and Gadd45 in JNK-dependent cell invasion, and provide insight for the roles of their human homologs in cancers.
背景
细胞侵袭是肿瘤转移的关键步骤，寻找其新的调节因子可为癌症治疗提供潜在的药物靶点。异常的GLYAT表达与人类癌症相关，但其在癌症中的作用尚不清楚。本研究旨在了解果蝇GLYAT在细胞侵袭中的功能和机制。
结果
我们发现dGLYAT调节Gadd45介导的JNK途径激活和细胞侵袭。首先，dGLYAT的缺失抑制了scrib缺失或Egr过表达诱导的JNK途径激活和侵袭性细胞迁移。其次，mRNA测序分析确定Gadd45是dGLYAT的潜在转录靶点，因为dGLYAT的缺失降低了Gadd45 mRNA水平。最后，Gadd45的敲低抑制了scrib缺失诱导的JNK途径激活和细胞侵袭。
结论
这些证据揭示了dGLYAT和Gadd45在依赖JNK的细胞侵袭中的作用，并为它们的人类同源物在癌症中的作用提供了见解。
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