ArticlePloS one2012
Epithelial-mesenchymal transition stimulates human cancer cells to extend microtubule-based invasive protrusions and suppresses cell growth in collagen gel.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 67 citations in OpenAlex.
- Extracellular HSP70/HSP70-PCs promote epithelial-mesenchymal transition of hepatocarcinoma cells.PloS one · 2013Trial
- The role of dynamic reciprocity in 3D cell migration: connecting cell and matrix mechanics to migratory plasticity.npj biological physics and mechanics · 2025Review
- Baicalin alleviates silica-induced lung inflammation and fibrosis by inhibiting TLR4/NF-?B pathway in rats.Physiological research · 2023Article
- Epithelial-to-Mesenchymal Transition-Related Markers in Prostate Cancer: From Bench to Bedside.Cancers · 2023Review
- Epithelial-Mesenchymal Transition Induced in Cancer Cells by Adhesion to Type I Collagen.International journal of molecular sciences · 2022Review
- Article
- Co-Stimulation of Oxytocin and Arginine-Vasopressin Receptors Affect Hypothalamic Neurospheroid Size.International journal of molecular sciences · 2021Article
- Collective cancer cell invasion in contact with fibroblasts through integrin-α5β1/fibronectin interaction in collagen matrix.Cancer science · 2020Article
- Mechanophenotyping of 3D multicellular clusters using displacement arrays of rendered tractions.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Snail-Overexpression Induces Epithelial-mesenchymal Transition and Metabolic Reprogramming in Human Pancreatic Ductal Adenocarcinoma and Non-tumorigenic Ductal Cells.Journal of clinical medicine · 2019Article
- Extracts of Celastrus Orbiculatus Inhibit Cancer Metastasis by Down-regulating Epithelial-Mesenchymal Transition in Hypoxia-Induced Human Hepatocellular Carcinoma Cells.Chinese journal of integrative medicine · 2019Article
- HDAC inhibitors promote intestinal epithelial regeneration via autocrine TGFβ1 signalling in inflammation.Mucosal immunology · 2019Article
- Cancer cell migration on elongate protrusions of fibroblasts in collagen matrix.Scientific reports · 2019Article
- Cyclin D1b Splice Variant Promotes αvβ3-mediated EMT Induced by LPS in Breast Cancer Cells.Current medical science · 2018Article
- Engineering 3D approaches to model the dynamic microenvironments of cancer bone metastasis.Bone research · 2018Review
- Candidate tumor suppressor ZNF154 suppresses invasion and metastasis in NPC by inhibiting the EMT via Wnt/β-catenin signalling.Oncotarget · 2017Article
- Mesenchymal Cell Invasion Requires Cooperative Regulation of Persistent Microtubule Growth by SLAIN2 and CLASP1.Developmental cell · 2016Article
- Dynamic Microenvironment Induces Phenotypic Plasticity of Esophageal Cancer Cells Under Flow.Scientific reports · 2016Article
- Scattering of Cell Clusters in Confinement.Biophysical journal · 2016Article
- Identification of SEC62 as a potential marker for 3q amplification and cellular migration in dysplastic cervical lesions.BMC cancer · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial-mesenchymal transition (EMT) is a crucial event in tumor invasion and metastasis. However, most of past EMT studies have been conducted in the conventional two-dimensional (2D) monolayer culture. Therefore, it remains unclear what invasive phenotypes are acquired by EMT-induced cancer cells. To address this point, we attempted to characterize EMT cells in more physiological, three-dimensional (3D) collagen gel culture. EMT was induced by treating three human carcinoma cell lines (A549, Panc-1 and MKN-1) with TGF-ß. The TGF-ß treatment stimulated these cells to overexpress the invasion markers laminin γ2 and MT1-MMP in 2D culture, in addition to the induction of well-known morphological change and EMT marker expression. EMT induction enhanced cell motility and adhesiveness to fibronectin and collagen in 2D culture. Although EMT cells showed comparable cell growth to control cells in 2D culture, their growth rates were extremely suppressed in soft agar and collagen gel cultures. Most characteristically, EMT-induced cancer cells commonly and markedly extended invasive protrusions in collagen gel. These protrusions were mainly supported by microtubules rather than actin cytoskeleton. Snail-introduced, stable EMT cells showed similar protrusions in 3D conditions without TGF-ß. Moreover, these protrusions were suppressed by colchicine or inhibitors of heat shock protein 90 (HSP-90) and protein phosphatase 2A. However, MMP inhibitors did not suppress the protrusion formation. These data suggest that EMT enhances tumor cell infiltration into interstitial stroma by extending microtubule-based protrusions and suppressing cell growth. The elevated cell adhesion to fibronectin and collagen and high cell motility also seem important for the tumor invasion.
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