ArticleCancer discovery2016
Tumor Cell-Driven Extracellular Matrix Remodeling Drives Haptotaxis during Metastatic Progression.
Article in Cancer discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed, 213 citations in OpenAlex.
- Extracellular Matrix Remodeling in Tumors: Forces Beyond Fibroblasts.Cancer research · 2026Article
- PLOD1 Drives Head and Neck Squamous Cell Carcinoma Progression Through P4HA2-Mediated Activation of the FAK/PI3K/AKT/mTOR Axis.Journal of cellular and molecular medicine · 2026Article
- Peptide concentration gradients and aligned microfiber topography synergize to speed and direct Schwann cell migration.Acta biomaterialia · 2026Article
- Astrocytes in neuroinflammation and brain cancer.Molecular biomedicine · 2026Review
- The Role of Actin-Binding Proteins in Breast Cancer Progression.Breast cancer (Dove Medical Press) · 2026Review
- The Role of Extracellular Proteases and Extracellular Matrix Remodeling in the Pre-Metastatic Niche.Biomolecules · 2025Review
- Macrophages migrate persistently and directionally upon entering 2D confinement in the presence of extracellular matrix.Biology open · 2025Article
- The type I collagen paradox in PDAC progression: microenvironmental protector turned tumor accomplice.Journal of translational medicine · 2025Review
- Macrophages migrate persistently and directionally upon entering 2D confinement in the presence of extracellular matrix.bioRxiv : the preprint server for biology · 2025Article
- Haptotactic Motion of Multivalent Vesicles Along Ligand-Density Gradients.Langmuir : the ACS journal of surfaces and colloids · 2025Article
- Inside a Metastatic Fracture: Molecular Bases and New Potential Therapeutic Targets.Cancer medicine · 2025Review
- Inhibiting fibronectin assembly in the breast tumor microenvironment increases cell death and improves response to doxorubicin.bioRxiv : the preprint server for biology · 2025Article
- Talin1 Ser425 phosphorylation promotes colorectal cancer progression and metastasis.Translational cancer research · 2025Article
- Neuronal mimicry in tumors: lessons from neuroscience to tackle cancer.Cancer metastasis reviews · 2025Review
- ECM-dependent regulation of septin 7 in focal adhesions promotes mechanosensing and functional response in fibroblasts.iScience · 2024Article
- Insights from a multiscale framework on metabolic rate variation driving glioblastoma multiforme growth and invasion.Communications engineering · 2024Article
- Pan-Cancer Analysis Reveals the Potential of PLOD1 as a Prognostic and Immune Biomarker for Human Cancer.Biomedicines · 2024Article
- The Role of eHsp90 in Extracellular Matrix Remodeling, Tumor Invasiveness, and Metastasis.Cancers · 2024Review
- Obesity Induces Temporally Regulated Alterations in the Extracellular Matrix That Drive Breast Tumor Invasion and Metastasis.Cancer research · 2024Article
- The mammalian actin elongation factor ENAH/MENA contributes to autophagosome formation via its actin regulatory function.Autophagy · 2024Article
66 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledFibronectin (FN) is a major component of the tumor microenvironment, but its role in promoting metastasis is incompletely understood. Here, we show that FN gradients elicit directional movement of breast cancer cells, in vitro and in vivo Haptotaxis on FN gradients requires direct interaction between α5β1 integrin and MENA, an actin regulator, and involves increases in focal complex signaling and tumor cell-mediated extracellular matrix (ECM) remodeling. Compared with MENA, higher levels of the prometastatic MENA(INV) isoform associate with α5, which enables 3-D haptotaxis of tumor cells toward the high FN concentrations typically present in perivascular space and in the periphery of breast tumor tissue. MENA(INV) and FN levels were correlated in two breast cancer cohorts, and high levels of MENA(INV) were significantly associated with increased tumor recurrence as well as decreased patient survival. Our results identify a novel tumor cell-intrinsic mechanism that promotes metastasis through ECM remodeling and ECM-guided directional migration. SIGNIFICANCE: Here, we provide new insight into how tumor cell:ECM interactions generate signals and structures that promote directed tumor cell migration, a critical component of metastasis. Our results identify a tumor cell-intrinsic mechanism driven by the actin regulatory protein MENA that promotes ECM remodeling and haptotaxis along FN gradients. Cancer Discov; 6(5); 516-31. ©2016 AACR.See related commentary by Santiago-Medina and Yang, p. 474This article is highlighted in the In This Issue feature, p. 461.
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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.