pERK transition-induced directional mode switching promotes epithelial tumor cell migration.

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  • Additional Information
    • Source:
      Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : National Academy of Sciences
    • Subject Terms:
      Cell Movement* ; rac1 GTP-Binding Protein*/metabolism ; rac1 GTP-Binding Protein*/genetics; Animals ; Humans ; Mice ; Cell Line, Tumor ; rhoA GTP-Binding Protein/metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Neoplasm Invasiveness ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; MAP Kinase Signaling System
    • Abstract:
      Increasing evidence suggests that tumor cells exhibit extreme plasticity in migration modes in order to adapt to microenvironments. However, the underlying mechanism for governing the migration mode switching is still unclear. Here, we revealed that epithelial tumor cells could develop a stable directional mode driven by hyperactivated ERK activity. This highly activated and dynamically changing ERK activity, called pERK transition, is crucial for inducing the switch from pauses state to directional movement and is also necessary for maintaining epithelial tumor cells in the directional mode. PERK transition integrated pERK surf, the dynamic and localized ERK activity at the leading edge. The sequential activation of RhoA and Rac1 by pERK transition played critical roles in generation of pERK surf activity through a movement feedback mechanism. PERK transition activity converted the orderly collective migration into the disordered dispersal movement, enhanced the invasiveness of epithelial tumor cells, and promoted their metastasis in immune-deficient mice. These findings revealed that the exquisite spatiotemporal organization of ERK activity orchestrates migration and invasion of tumor cells and provide evidence for the mechanism underlying migration mode switching in epithelial tumor cells.
      Competing Interests: Competing interests statement:The authors declare no competing interest.
    • Grant Information:
      31970729 National Natural Science Funds of the People's Republic of China; JCYJ20180507182239272 Shenzhen Science and technology innovation committee project; KQTD20190929172538530 Shenzhen Science and Technology Program
    • Contributed Indexing:
      Keywords: migration mode switching; migration plasticity; pERK surf; pERK transition; rampage mode
    • Accession Number:
      EC 3.6.5.2 (rac1 GTP-Binding Protein)
      EC 3.6.5.2 (rhoA GTP-Binding Protein)
      EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
      0 (RAC1 protein, human)
    • Publication Date:
      Date Created: 20241213 Date Completed: 20241213 Latest Revision: 20241213
    • Publication Date:
      20241214
    • Accession Number:
      10.1073/pnas.2318871121
    • Accession Number:
      39671185