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Cited by 202Cellular Mechanics and InteractionsProtein Kinase Regulation and GTPase SignalingMicrotubule and mitosis dynamics

The Arp2/3 regulatory system and its deregulation in cancer

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Molinie, Nicolas, Gautreau, Alexis·2018·Physiological Reviews
DOI 10.1152/physrev.00006.2017
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Abstract

The Arp2/3 complex is an evolutionary conserved molecular machine that generates branched actin networks. When activated, the Arp2/3 complex contributes the actin branched junction and thus cross-links the polymerizing actin filaments in a network that exerts a pushing force. The different activators initiate branched actin networks at the cytosolic surface of different cellular membranes to promote their protrusion, movement, or scission in cell migration and membrane traffic. Here we review the structure, function, and regulation of all the direct regulators of the Arp2/3 complex that induce or inhibit the initiation of a branched actin network and that controls the stability of its branched junctions. Our goal is to present recent findings concerning novel inhibitory proteins or the regulation of the actin branched junction and place these in the context of what was previously known to provide a global overview of how the Arp2/3 complex is regulated in human cells. We focus on the human set of Arp2/3 regulators to compare normal Arp2/3 regulation in untransformed cells to the deregulation of the Arp2/3 system observed in patients affected by various cancers. In many cases, these deregulations promote cancer progression and have a direct impact on patient survival.

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  • The ARP2/3 complex is a critical mediator of the entire metastatic cascade, from migration to invasion and in vivo metastatic spread.

    “The ARP2/3 complex is a critical mediator of the entire metastatic cascade; from migration to invasion and in vivo metastatic spread (Molinie & Gautreau, 2018, Mondal et al., 2021).”

    From SHARPIN S146 phosphorylation mediates ARP2/3 interaction, cancer cell invasion and metastasis (2022) · cites this paper as Molinie & Gautreau, 2018

    Section C, “The Arp2/3 Complex in Cancer” (page unavailable), links Arp2/3 to cancer-cell migration and invasion, and says Arp2/3-mediated migration helps colorectal carcinoma cells seed metastases. This supports the named processes, but the claim that Arp2/3 is a critical mediator of the entire metastatic cascade extends beyond what the passage establishes. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • ARP2/3-dependent lamellipodia formation promotes cell migration and invasion.

    “ARP2/3-dependent lamellipodia formation promotes cell migration and invasion (Molinie & Gautreau, 2018, Mondal et al., 2021, Suraneni, Rubinstein et al., 2012).”

    From SHARPIN S146 phosphorylation mediates ARP2/3 interaction, cancer cell invasion and metastasis (2022) · cites this paper as Molinie & Gautreau, 2018

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Cited by

Sorted by citations

Authors
Molinie, N., & Gautreau, A.
Affiliations
  • Ecole Polytechnique, Université Paris-Saclay, CNRS UMR 7654, Palaiseau, France; and Moscow Institute of Physics and Technology, Life Sciences Center, Dolgoprudny, Russia
  • Centre National de la Recherche Scientifique (FR)
ORCID
Gautreau, Alexis
Venue
Physiological Reviews
Publisher
American Physiological Society
Published
2018-01-01
Volume
98
Issue
1
Pages
215-238
ISSN
  • 0031-9333 (ISSN-L)
  • 1522-1210
DOI
10.1152/physrev.00006.2017
OpenAlex
W2774074031
Cited by
202
References
4
Citations by year
2026: 12 · 2025: 13 · 2024: 21 · 2023: 36 · 2022: 24 · 2021: 44 · 2020: 20 · 2019: 23 · 2018: 8 · 2017: 1
FWCI
1.66
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Physiological Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Agence Nationale de la Recherche (L' Agence Nationale de la Recherche) (ANR-15-CE13-0016-01)
  • Fondation ARC pour la Recherche sur le Cancer (Fondation ARC) (PGA120140200831)
  • Institut National du Cancer (INCA_6521)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
Arp2/3 complex, branched actin networks, actin cytoskeleton regulation, tumor progression, tumor cell migration, membrane traffic
MeSH terms
Actins, Amino Acid Sequence, Animals, Cell Movement, Humans, Actin Cytoskeleton, Neoplasms, Actin-Related Protein 2-3 Complex

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