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Emerging roles of deubiquitinating enzymes in actin cytoskeleton and tumor metastasis

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Abstract

Background

Metastasis accounts for the majority of cancer-related deaths. Actin dynamics and actin-based cell migration and invasion are important factors in cancer metastasis. Metastasis is characterized by actin polymerization and depolymerization, which are precisely regulated by molecular changes involving a plethora of actin regulators, including actin-binding proteins (ABPs) and signalling pathways, that enable cancer cell dissemination from the primary tumour. Research on deubiquitinating enzymes (DUBs) has revealed their vital roles in actin dynamics and actin-based migration and invasion during cancer metastasis.

Conclusion

Here, we review how DUBs drive tumour metastasis by participating in actin rearrangement and actin-based migration and invasion. We summarize the well-characterized and essential actin cytoskeleton signalling molecules related to DUBs, including Rho GTPases, Src kinases, and ABPs such as cofilin and cortactin. Other DUBs that modulate actin-based migration signalling pathways are also discussed. Finally, we discuss and address therapeutic opportunities and ongoing challenges related to DUBs with respect to actin dynamics.

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Funding

This review was supported by Key Research and Development Plan of Shandong Province (2022CXGC020501), Taishan Scholar Foundation of Shandong Province (tsqnz20230632) and National Natural Science Foundation of China (8230101506).

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  1. Ying Xue and Cong Xue are first authors.

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  1. Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, PR China

    Ying Xue & Wei Song

  2. School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, PR China

    Cong Xue

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Y.X writed the review article. W.S edited the review. C.X constructed the figure. All authors have read and agreed to the published version of the manuscript.

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Xue, Y., Xue, C. & Song, W. Emerging roles of deubiquitinating enzymes in actin cytoskeleton and tumor metastasis. Cell Oncol. (2024). https://doi.org/10.1007/s13402-024-00923-z

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