ArticleOncogene2015
NEDD9/Arf6-dependent endocytic trafficking of matrix metalloproteinase 14: a novel mechanism for blocking mesenchymal cell invasion and metastasis of breast cancer.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The trial behind it
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Invadopodia in cancer metastasis: dynamics, regulation, and targeted therapies.Journal of translational medicine · 2025Review
- Potential target within the tumor microenvironment - MT1-MMP.Frontiers in immunology · 2025Review
- Membrane trafficking alterations in breast cancer progression.Frontiers in cell and developmental biology · 2024Review
- PTEN deficiency exposes a requirement for an ARF GTPase module for integrin-dependent invasion in ovarian cancer.The EMBO journal · 2023Article
- Cytoplasmic Tail of MT1-MMP: A Hub of MT1-MMP Regulation and Function.International journal of molecular sciences · 2023Review
- Structural Insights Uncover the Specific Phosphoinositide Recognition by the PH1 Domain of Arap3.International journal of molecular sciences · 2023Article
- Identification of ARAP3 as a regulator of tumor progression, macrophage infiltration and osteoclast differentiation in a tumor microenvironment-related prognostic model of Ewing sarcoma.American journal of cancer research · 2023Article
- Review
- Vesicular trafficking-related proteins as the potential therapeutic target for breast cancer.Protoplasma · 2020Review
- ZMYND10, an epigenetically regulated tumor suppressor, exerts tumor-suppressive functions via miR145-5p/NEDD9 axis in breast cancer.Clinical epigenetics · 2019Article
- APE1 Upregulates MMP-14 via Redox-Sensitive ARF6-Mediated Recycling to Promote Cell Invasion of Esophageal Adenocarcinoma.Cancer research · 2019Article
- CLIC4 regulates late endosomal trafficking and matrix degradation activity of MMP14 at focal adhesions in RPE cells.Scientific reports · 2019Article
- MT1-MMP-dependent cell migration: proteolytic and non-proteolytic mechanisms.Biochemical Society transactions · 2019Review
- A NUMB-EFA6B-ARF6 recycling route controls apically restricted cell protrusions and mesenchymal motility.The Journal of cell biology · 2018Article
- Sphingolipids inhibit endosomal recycling of nutrient transporters by inactivating ARF6.Journal of cell science · 2018Article
- LPA signaling is regulated through the primary cilium: a novel target in glioblastoma.Oncogene · 2018Article
- HDAC3-mediated silencing of miR-451 decreases chemosensitivity of patients with metastatic castration-resistant prostate cancer by targeting NEDD9.Therapeutic advances in medical oncology · 2018Article
- Progesterone and calcitriol reduce invasive potential of endometrial cancer cells by targeting ARF6, NEDD9 and MT1-MMP.Oncotarget · 2017Article
- Tumor microenvironment heterogeneity: challenges and opportunities.Current molecular biology reports · 2017Article
- Overexpression of NEDD9 in renal cell carcinoma is associated with tumor migration and invasion.Oncology letters · 2017Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
NEDD9 is an established marker of invasive and metastatic cancers. NEDD9 downregulation has been shown to dramatically reduce cell invasion and metastasis in multiple tumors. The mechanisms by which NEDD9 regulates invasion are largely unknown. In the current study, we have found that NEDD9 is required for matrix metalloproteinase 14 (MMP14) enzymatic recovery/recycling through the late endosomes to enable disengagement of tissue inhibitor of matrix metalloproteinase 2 (TIMP2) and tumor invasion. Depletion of NEDD9 decreases targeting of the MMP14/TIMP2 complex to late endosomes and increases trafficking of MMP14 from early/sorting endosomes back to the surface in a small GTPase ADP ribosylation factor-6 (Arf6)-dependent manner. NEDD9 directly binds to Arf6-GTPase-activating protein, ARAP3 and Arf6-effector GGA3, thereby facilitating the Arf6 inactivation required for MMP14/TIMP2 targeting to late endosomes. Re-expression of NEDD9 or a decrease in Arf6 activity is sufficient to restore MMP14 activity and the invasive properties of tumor cells. Importantly, NEDD9 inhibition by Vivo-Morpholinos, an antisense therapy, decreases primary tumor growth and metastasis in xenograft models of breast cancer. Collectively, our findings uncover a novel mechanism to control tumor-cell dissemination through NEDD9/Arf6-dependent regulation of MMP14/TIMP2 trafficking, and validate NEDD9 as a clinically relevant therapeutic target to treat metastatic cancer.
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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.