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Cited by 80Angiogenesis and VEGF in CancerLymphatic System and DiseasesMathematical Biology Tumor Growth

VEGFR1 promotes cell migration and proliferation through PLCγ and PI3K pathways

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Weddell, Jared C., Chen, Si, Imoukhuede, P. I.·2017·npj Systems Biology and Applications
DOI 10.1038/s41540-017-0037-9PMC PMC5736688
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Abstract

The ability to control vascular endothelial growth factor (VEGF) signaling offers promising therapeutic potential for vascular diseases and cancer. Despite this promise, VEGF-targeted therapies are not clinically effective for many pathologies, such as breast cancer. VEGFR1 has recently emerged as a predictive biomarker for anti-VEGF efficacy, implying a functional VEGFR1 role beyond its classically defined decoy receptor status. Here we introduce a computational approach that accurately predicts cellular responses elicited via VEGFR1 signaling. Aligned with our model prediction, we show empirically that VEGFR1 promotes macrophage migration through PLC γ and PI3K pathways and promotes macrophage proliferation through a PLC γ pathway. These results provide new insight into the basic function of VEGFR1 signaling while offering a computational platform to quantify signaling of any receptor.

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  • A link between PLCγ enzymes, cytoskeletal changes and cell motility has been previously documented.

    “A link between PLCγ enzymes, cytoskeletal changes and cell motility has been previously documented [for example (Obst et al., 2021;Weddell et al., 2018)] and in the context of microglia could be important for other functions that are relevant for AD, for example, for phagocytosis and removal of amyloid fibres.”

    From Characterisation of molecular mechanisms for PLCγ2 disease-linked variants (2024) · cites this paper as Weddell et al., 2018

    The Discussion reports that VEGFR1-induced PLCγ activation is required for macrophage migration, supporting the PLCγ–cell motility link. It does not directly document cytoskeletal changes as part of that link; cytoskeletal reorganization appears in the title of a work listed in the References, not as a finding reported for PLCγ in this paper. The later suggestion about microglial phagocytosis is the citing authors’ own framing. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Weddell, J. C., Chen, S., & Imoukhuede, P. I.
Affiliations
University of Illinois Urbana-Champaign (US)
Corresponding author
Imoukhuede, P. I.
ORCID
Venue
npj Systems Biology and Applications
Publisher
Springer Science and Business Media LLC
Published
2017-12-19
Volume
4
Issue
1
Pages
1-1
ISSN
2056-7189 (ISSN-L)
DOI
10.1038/s41540-017-0037-9
PMC
PMC5736688
OpenAlex
W2771551779
Cited by
80
References
1
Citations by year
2026: 5 · 2025: 14 · 2024: 5 · 2023: 11 · 2022: 10 · 2021: 12 · 2020: 8 · 2019: 11 · 2018: 4
FWCI
2.57
Type
journal article
Language
en
Open access
Licence
Locations
  • npj Systems Biology and Applications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Science Foundation (1512598)
  • American Cancer Society (282802)
  • American Heart Association (16SDG26940002)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
Keywords
VEGFR1, VEGF signaling, PI3K signaling, macrophage migration, macrophage proliferation, anti-VEGF therapy, predictive biomarkers, breast cancer, receptor signaling

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