Emerging roles of deubiquitinating enzymes in actin cytoskeleton and tumor metastasis

去泛素化酶在肌动蛋白细胞骨架和肿瘤转移中的新兴作用

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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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