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Extracellular matrix protein-1 secretory isoform promotes ovarian cancer through increasing alternative mRNA splicing and stemness

Author

Listed:
  • Huijing Yin

    (Fudan University Shanghai Cancer Center
    Fudan University)

  • Jingshu Wang

    (Fudan University)

  • Hui Li

    (Fudan University)

  • Yinjue Yu

    (Fudan University)

  • Xiaoling Wang

    (Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine)

  • Lili Lu

    (Fudan University Shanghai Cancer Center
    Fudan University)

  • Cuiting Lv

    (Fudan University)

  • Bin Chang

    (Fudan University
    Fudan University Shanghai Cancer Center)

  • Wei Jin

    (The People’s Hospital of Guangxi Zhuang Autonomous Region)

  • Wenwen Guo

    (Fudan University
    Fudan University Shanghai Cancer Center)

  • Chunxia Ren

    (Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine)

  • Gong Yang

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

Abstract

Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet to be clarified. We report in this study that the secretory ECM1a isoform induces tumorigenesis through the GPR motif binding to integrin αXβ2 and the activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP binding cassette subfamily G member 1 (ABCG1) transduces the ECM1a-integrin αXβ2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cancer cell cisplatin resistance through up-regulation of the CD326-mediated cell stemness. On the contrary, the non-secretory ECM1b isoform binds myosin and blocks its phosphorylation, impairing cytoskeleton-mediated signaling and tumorigenesis. Moreover, ECM1a induces the expression of the heterogeneous nuclear ribonucleoprotein L like (hnRNPLL) protein to favor the alternative mRNA splicing generating ECM1a. ECM1a, αXβ2, ABCG1 and hnRNPLL higher expression associates with poor survival, while ECM1b higher expression associates with good survival. These results highlight ECM1a, integrin αXβ2, hnRNPLL and ABCG1 as potential targets for treating cancers associated with ECM1-activated signaling.

Suggested Citation

  • Huijing Yin & Jingshu Wang & Hui Li & Yinjue Yu & Xiaoling Wang & Lili Lu & Cuiting Lv & Bin Chang & Wei Jin & Wenwen Guo & Chunxia Ren & Gong Yang, 2021. "Extracellular matrix protein-1 secretory isoform promotes ovarian cancer through increasing alternative mRNA splicing and stemness," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24315-1
    DOI: 10.1038/s41467-021-24315-1
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    Cited by:

    1. Yuchao Xia & Zijie Jin & Chengsheng Zhang & Linkun Ouyang & Yuhao Dong & Juan Li & Lvze Guo & Biyang Jing & Yang Shi & Susheng Miao & Ruibin Xi, 2023. "TAGET: a toolkit for analyzing full-length transcripts from long-read sequencing," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Keyang Xu & Ai Fu & Zhaoyi Li & Liangbin Miao & Zhonghan Lou & Keying Jiang & Condon Lau & Tao Su & Tiejun Tong & Jianfeng Bao & Aiping Lyu & Hiu Yee Kwan, 2024. "Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Zihan Tang & Yanyan Xu & Yun Tan & Hui Shi & Peipei Jin & Yunqi Li & Jialin Teng & Honglei Liu & Haoyu Pan & Qiongyi Hu & Xiaobing Cheng & Junna Ye & Yutong Su & Yue Sun & Jianfen Meng & Zhuochao Zhou, 2023. "CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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