PLK1 phosphorylates RhoGDI1 and promotes cancer cell migration and invasion

Jeewon Lim1,2, Yo Sep Hwang1, Hyang Ran Yoon1

  • 1Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.

Cancer Cell International
|February 14, 2024
PubMed
Abstract

Insights

Polo-like kinase 1 (PLK1) phosphorylates Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1), promoting cancer cell migration and invasion via RhoA activation. This interaction offers potential therapeutic targets for cancer progression.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1) regulates Rho GTPase activity, crucial for cellular processes like migration.
  • Phosphorylation of RhoGDI1 influences Rho GTPase activation during cell migration.

Purpose of the Study:

  • Identify novel kinases phosphorylating RhoGDI1.
  • Investigate the mechanism linking RhoGDI1-PLK1 interaction to cancer cell migration.

Main Methods:

  • Protein interaction assays (Immunoprecipitation, GST pull-down, PLA).
  • In vitro kinase assays and RhoA activation assays.
  • Cell migration and invasion assays (Transwell), including in vivo metastasis models.

Main Results:

  • Polo-like kinase 1 (PLK1) directly interacts with RhoGDI1.
  • PLK1 phosphorylates RhoGDI1 at Thr7 and Thr91, enhancing cell motility.
  • Mutant RhoGDI1 (aa 90-111) inhibited PLK1 interaction, attenuated RhoA activation, and reduced cancer cell migration, invasion, and metastasis.

Conclusions:

  • PLK1-mediated phosphorylation of RhoGDI1 promotes cancer cell migration and invasion by activating RhoA.
  • The PLK1-RhoGDI1 interaction is linked to malignant progression, suggesting therapeutic potential.

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