dGLYAT modulates Gadd45-mediated JNK activation and cell invasion

Meng Xu; Pu Ren; Juhui Tian; Lisha Xiao; Ping Hu; Ping Chen; Wenzhe Li; Lei Xue

doi:10.1186/s13008-022-00080-5

dGLYAT modulates Gadd45-mediated JNK activation and cell invasion

Cell Div. 2022 Aug 6;17(1):4. doi: 10.1186/s13008-022-00080-5.

Authors

Meng Xu¹, Pu Ren², Juhui Tian¹, Lisha Xiao¹, Ping Hu¹, Ping Chen¹, Wenzhe Li³, Lei Xue^{4

5}

Affiliations

¹ The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai, China.
² The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai, China. ren_pu123@qq.com.
³ The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai, China. lwz@tongji.edu.cn.
⁴ The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai, China. lei.xue@tongji.edu.cn.
⁵ 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. lei.xue@tongji.edu.cn.

Abstract

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.

Keywords: Cell invasion; Drosophila; Gadd45; JNK; dGLYAT.

Abstract

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