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Therapeutic potential of targeting the NEDD4L-eEF1A1 axis in cancer therapy

Yan Qin1,2,3,4, Xinyue Wang2, Minghui Zhao4,5

  • 1Central Laboratory, Affiliated Hospital of Hebei University, Baoding 071000, China.

Acta Biochimica Et Biophysica Sinica
|June 26, 2025
PubMed

Insights

Neuronal precursor cell expression developmentally downregulated 4-like (NEDD4L) inhibits tumor angiogenesis by degrading eEF1A1 in endothelial cells. Loss of NEDD4L promotes tumor growth and angiogenesis, highlighting the NEDD4L-eEF1A1 axis as a therapeutic target.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Endothelial cell proliferation and migration are critical for tumor angiogenesis.
  • Neuronal precursor cell expression developmentally downregulated 4-like (NEDD4L), an E3 ubiquitin ligase, is implicated in tumorigenesis.
  • The specific functions of NEDD4L in endothelial cells and tumor angiogenesis require elucidation.

Purpose of the Study:

  • To investigate the role of NEDD4L in human umbilical vein endothelial cell (HUVEC) function.
  • To determine the impact of NEDD4L on tumor angiogenesis.
  • To elucidate the molecular mechanisms underlying NEDD4L's function in endothelial cells.

Main Methods:

  • Overexpression of NEDD4L in HUVECs.
  • Assessment of cell proliferation and migration assays.
  • Analysis of autophagic activity.
  • Proteomic profiling and ubiquitination assays to identify interacting proteins and ubiquitination patterns.
  • In vivo studies using mouse models to evaluate tumor growth and angiogenesis.

Main Results:

  • NEDD4L overexpression suppressed HUVEC proliferation and migration.
  • Autophagic activity was increased in NEDD4L-overexpressing cells.
  • NEDD4L was found to interact with and promote K48-linked ubiquitination-mediated degradation of eEF1A1.
  • Loss of endothelial NEDD4L significantly enhanced tumor growth and angiogenesis in vivo.

Conclusions:

  • NEDD4L inhibits tumor angiogenesis by regulating eEF1A1 ubiquitination and degradation.
  • The NEDD4L-eEF1A1 axis is a key regulator of endothelial cell function and tumor angiogenesis.
  • NEDD4L represents a potential therapeutic target for inhibiting tumor angiogenesis.
Keywords:
NEDD4LangiogenesisautophagyeEF1A1migrationproliferationubiquitination

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