ArticleMolecular cancer research : MCR2017
Dual Targeting of Mesenchymal and Amoeboid Motility Hinders Metastatic Behavior.
Article in Molecular cancer research : MCR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Migrastatic therapy as a potential game-changer in adaptive cancer treatment.Scientific reports · 2026Article
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- Mechanical signatures in cancer metastasis.npj biological physics and mechanics · 2025Review
- Review
- Inhibition of MMPs supports amoeboid angiogenesis hampering VEGF-targeted therapies via MLC and ERK 1/2 signaling.Journal of translational medicine · 2023Article
- NEDD9 Restrains dsDNA Damage Response during Non-Small Cell Lung Cancer (NSCLC) Progression.Cancers · 2022Article
- Article
- Morphodynamics facilitate cancer cells to navigate 3D extracellular matrix.Scientific reports · 2021Article
- Article
- Adhesion of Triple-Negative Breast Cancer Cells under Fluorescent and Soft X-ray Contact Microscopy.International journal of molecular sciences · 2021Article
- Reduced WNT5A signaling in melanoma cells favors an amoeboid mode of invasion.Molecular oncology · 2021Article
- Actin dynamics during tumor cell dissemination.International review of cell and molecular biology · 2021Review
- Recent advances in understanding the role of metabolic heterogeneities in cell migration.Faculty reviews · 2021Review
- Plasticity of cancer cell invasion: Patterns and mechanisms.Translational oncology · 2021Review
- Superior breast cancer metastasis risk stratification using an epithelial-mesenchymal-amoeboid transition gene signature.Breast cancer research : BCR · 2020Article
- Targeting Rac and Cdc42 GEFs in Metastatic Cancer.Frontiers in cell and developmental biology · 2020Review
- The Role of Microenvironmental Cues and Mechanical Loading Milieus in Breast Cancer Cell Progression and Metastasis.Frontiers in bioengineering and biotechnology · 2020Review
- Multinucleation of Incubated Cells and Their Morphological Differences Compared to Mononuclear Cells.Micromachines · 2019Article
- SOX2 promotes hypoxia-induced breast cancer cell migration by inducing NEDD9 expression and subsequent activation of Rac1/HIF-1α signaling.Cellular & molecular biology letters · 2019Article
- NEDD9 Facilitates Hypoxia-Induced Gastric Cancer Cell Migration via MICAL1 Related Rac1 Activation.Frontiers in pharmacology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Commonly upregulated in human cancers, the scaffolding protein NEDD9/HEF1 is a known regulator of mesenchymal migration and cancer cell plasticity. However, the functional role of NEDD9 as a regulator of different migration/invasion modes in the context of breast cancer metastasis is currently unknown. Here, it is reported that NEDD9 is necessary for both mesenchymal and amoeboid individual cell migration/invasion in triple-negative breast cancer (TNBC). NEDD9 deficiency results in acquisition of the amoeboid morphology, but severely limits all types of cell motility. Mechanistically, NEDD9 promotes mesenchymal migration via VAV2-dependent Rac1 activation, and depletion of VAV2 impairs the ability of NEDD9 to activate Rac1. In addition, NEDD9 supports a mesenchymal phenotype through stimulating polymerization of actin via promoting CTTN phosphorylation in an AURKA-dependent manner. Interestingly, an increase in RhoA activity in NEDD9-depleted cells does not facilitate a switch to functional amoeboid motility, indicating a role of NEDD9 in the regulation of downstream RhoA signaling effectors. Simultaneous depletion of NEDD9 or inhibition of AURKA in combination with inhibition of the amoeboid driver ROCK results in an additional decrease in cancer cell migration/invasion. Finally, we confirmed that a dual targeting strategy is a viable and efficient therapeutic approach to hinder the metastasis of breast cancer in xenograft models, showcasing the important need for further clinical evaluation of this regimen to impede the spread of disease and improve patient survival.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.