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TM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis

Author

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  • Zhaoyue Meng

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Zhichao Li

    (The Chinese University of Hong Kong
    The First Affiliated Hospital of Shenzhen University)

  • Mingxu Xie

    (The Chinese University of Hong Kong)

  • Hongyan Yu

    (The Chinese University of Hong Kong)

  • Liwen Jiang

    (The Chinese University of Hong Kong)

  • Xiaoqiang Yao

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

Abstract

F-actin dynamics is crucial for many fundamental properties of cancer cells, from cell-substrate adhesion to migration, invasion and metastasis. However, the regulatory mechanisms of actin dynamics are still incompletely understood. In this study, we demonstrate the function of a protein named TM9SF4 in regulating actin dynamics and controlling cancer cell motility and metastasis. We show that an N-terminal fragment (NTF) cleaved from TM9SF4 can directly bind to F-actin to induce actin oxidation at Cys374, consequently enhancing cofilin-mediated F-actin disassembly. Knockdown of TM9SF4 reduces cell migration and invasion in ovarian cancer cells A2780, SKOV3 and several high grade serous ovarian cancer lines (HGSOCs). In vivo, knockdown of TM9SF4 completely abolishes the tumor growth and metastasis in athymic nude mice. These data provide mechanistic insights into TM9SF4-mediated regulation of actin dynamics in ovarian cancer cells.

Suggested Citation

  • Zhaoyue Meng & Zhichao Li & Mingxu Xie & Hongyan Yu & Liwen Jiang & Xiaoqiang Yao, 2022. "TM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33276-y
    DOI: 10.1038/s41467-022-33276-y
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    References listed on IDEAS

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    1. Xiao Hu & Zongzhi Z. Liu & Xinyue Chen & Vincent P. Schulz & Abhishek Kumar & Amaleah A. Hartman & Jason Weinstein & Jessica F. Johnston & Elisa C. Rodriguez & Anna E. Eastman & Jijun Cheng & Liz Min , 2019. "MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
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