NEDD9-Dependent Mechanisms in Cancer Metastasis

Neural precursor cell expressed developmentally downregulated protein 9 (NEDD9) serves as a multifunctional scaffolding protein that integrates signals from integrins, growth factor receptors and intracellular kinases to coordinate cytoskeletal remodelling, adhesion dynamics and transcriptional programmes. Upregulation of NEDD9 has been observed across a spectrum of malignancies, where it promotes detachment from the primary tumour, invasion through stromal barriers and survival in the circulation. Mechanistically, NEDD9 localises to focal adhesions and invadopodia, where it organises actin polymerisation and matrix degradation via interactions with kinases such as FAK and SRC. Concurrently, NEDD9 influences downstream pathways including RAC1 GTPase activation, AKT/mTOR signalling and ERK-driven transcriptional networks, thereby reinforcing epithelial–mesenchymal transition, motility and resistance to apoptosis. These intertwined processes underpin the ability of cancer cells to traverse extracellular matrices, intravasate and establish secondary growths at distant sites. Emerging evidence also implicates NEDD9 in the modulation of tumour–stroma crosstalk and mechanotransduction, further emphasising its central role in metastatic progression and its potential as a therapeutic target.

Research from Nature Portfolio

No recent Nature Portfolio content available.

NEDD9-Dependent Mechanisms in Cancer Metastasis publication trend

The graph below shows the total number of articles in nedd9-dependent mechanisms in cancer metastasis across all publications each year (not limited to Nature Index journals).

Technical terms

NEDD9: A scaffolding protein that organises cytoskeletal assemblies and adhesion complexes to regulate cell migration and invasion.

Epithelial–mesenchymal transition: A cellular programme in which epithelial cells acquire mesenchymal traits, enhancing motility and invasiveness.

Invadopodia: Actin-rich protrusions that focus proteolytic enzymes to degrade extracellular matrix and facilitate invasion.

RAC1: A small GTPase that controls actin cytoskeleton dynamics and lamellipodia formation.

AKT/mTOR pathway: A signalling cascade that promotes cell growth, survival and metabolism in response to extracellular cues.

MICAL1: An oxidoreductase that modulates actin filament dynamics and contributes to cell motility.

References

1. Transcription factor 7 like 2 promotes metastasis in hepatocellular carcinoma via NEDD9-mediated activation of AKT/mTOR signaling pathway. Molecular Medicine (2024).
2. NEDD9 Facilitates Hypoxia-Induced Gastric Cancer Cell Migration via MICAL1 Related Rac1 Activation. Frontiers in Pharmacology (2019).
3. NEDD9 Is a Positive Regulator of Epithelial-Mesenchymal Transition and Promotes Invasion in Aggressive Breast Cancer. PLOS ONE (2011).