PDK1 Regulates Cancer Cell Motility by Antagonising Inhibition of ROCK1 by RhoE
Abstract
In three-dimensional matrices cancer cells move with a rounded, amoeboid morphology that is controlled by ROCK-dependent contraction of acto-myosin. In this study, we show that PDK1 is required for phosphorylation of myosin light chain and cell motility, both on deformable gels and in vivo. Depletion of PDK1 alters the localization of ROCK1 and reduces its ability to drive cortical acto-myosin contraction. This form of ROCK1 regulation does not require PDK1 kinase activity, but instead involves direct binding of PDK1 to ROCK1 at the plasma membrane; PDK1 competes directly with RhoE for binding to ROCK1. In the absence of PDK1, negative regulation by RhoE predominates, causing reduced acto-myosin contractility and motility. This work uncovers a novel non-catalytic role for PDK1 in regulating cortical acto-myosin and cell motility.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Localization of PDK1 to the membrane is crucial for dissociation of the inhibitory RhoE/ROCK1 complex.
“The localization of PDK1 to the membrane is crucial for the dissociation of the inhibitory RhoE/ROCK1 complex [55].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [55]
Upon activation of cell migration, RhoE dissociates from ROCK1, allowing ROCK1 to phosphorylate MLC, promoting actin polymerization.
“Upon activation of cell migration, RhoE dissociates from ROCK1, allowing ROCK1 to phosphorylate MLC, which promotes actin polymerization and facilitates cell movement.”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [55]
Loss of IPMK's lipid kinase activity disrupts PDK1 localization, stabilizing the ROCK1/RhoE inhibitory complex and preventing ROCK1-mediated MLC phosphorylation, thus hindering cell migration.
“The loss of IPMK’s lipid kinase activity disrupts PDK1 localization, stabilizing the ROCK1/RhoE inhibitory complex and preventing ROCK1-mediated MLC phosphorylation [55], thus hindering cell migration (Figure 3B-i).”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [55]
The interaction between RhoE and ROCK1 inhibits ROCK1's ability to phosphorylate MLC, preventing cell migration.
“At the molecular level, the interaction between RhoE and ROCK1 inhibits ROCK1’s ability to phosphorylate MLC, thereby preventing cell migration.”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [55]
Cited by
Sorted by citations
Rho-associated coiled-coil containing kinases (ROCK): Structure, regulation, and functions
Julian, L., & Olson, M. F. (2014) · Small GTPases · doi:10.4161/sgtp.29846 · Cited by 550 · see citing works
Induction of entosis by epithelial cadherin expression
Sun, Q., Cibas, E. S., Huang, H., Hodgson, L., & Overholtzer, M. (2014) · Cell Research · doi:10.1038/cr.2014.137 · Cited by 148 · see citing works
From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease
Mishra, S. H., Chatterjee, S., Viera-Preval, L., & Guha, P. (2025) · Biomolecules · doi:10.3390/biom15091266 · Cited by 1 · see citing works
“The loss of IPMK’s lipid kinase activity disrupts PDK1 localization, stabilizing the ROCK1/RhoE inhibitory complex and preventing ROCK1-mediated MLC phosphorylation [55], thus hindering cell migration (Figure 3B-i).”
- Authors
- Pinner, S., & Sahai, E.
- Affiliations
- Cancer Research UK (GB)
- Corresponding author
- Sahai, Erik
- ORCID
- Sahai, Erik
- Venue
- Nature Cell Biology
- Published
- 2008-01-20
- Volume
- 10
- Issue
- 2
- Pages
- 127-137
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2055800277
- Cited by
- 267
- References
- 0
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 7 · 2023: 14 · 2022: 8 · 2021: 10 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 18 · 2016: 21 · 2015: 17 · 2014: 12 · 2013: 16 · 2012: 27
- FWCI
- 11.60
- Type
- journal article
- Language
- en
- Update notices
- erratum (2008-03-01)
- Open access
- closed
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Cancer Research UK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- PDK1, ROCK1, RhoE, tumor cell motility, amoeboid movement, actomyosin contractility, myosin light chain phosphorylation, protein-protein interaction, three-dimensional matrix
- MeSH terms
- Pyruvate Dehydrogenase Acetyl-Transferring Kinase, Actins, Cell Membrane, Cell Movement, Humans, Phosphorylation, Protein Binding, Pseudopodia, Protein Serine-Threonine Kinases, Myosin Light Chains, rho GTP-Binding Proteins, Cell Line, Tumor, Cell Shape, rho-Associated Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
