ArticleCancer research2018
A Soft Microenvironment Protects from Failure of Midbody Abscission and Multinucleation Downstream of the EMT-Promoting Transcription Factor Snail.
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Large-scale and high-resolution mass spectrometry-based proteomics defines molecular subtypes of nasopharyngeal carcinoma for therapeutic targeting.Signal transduction and targeted therapy · 2026Article
- Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease.Journal of translational medicine · 2025Review
- Retracted article: Knockdown of long non-coding RNA AGAP2-AS1 suppresses the proliferation and metastasis of glioma by targeting microRNA-497-5p.Bioengineered · 2024Article
- A comprehensive overview of metaplastic breast cancer: Features and treatments.Cancer science · 2024Review
- The concerted action of SEPT9 and EPLIN modulates the adhesion and migration of human fibroblasts.Life science alliance · 2024Article
- Capsaicin and Cold exposure promote EMT-mediated premetastatic niche formation to facilitate colorectal cancer metastasis.Journal of Cancer · 2024Article
- Septins as membrane influencers: direct play or in association with other cytoskeleton partners.Frontiers in cell and developmental biology · 2023Review
- ECM stiffness modulates the proliferation but not the motility of primary corneal keratocytes in response to PDGF-BB.Experimental eye research · 2022Article
- Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors.Cancers · 2022Review
- Substratum stiffness signals through integrin-linked kinase and β1-integrin to regulate midbody proteins and abscission during EMT.Molecular biology of the cell · 2021Article
- Septins, a cytoskeletal protein family, with emerging role in striated muscle.Journal of muscle research and cell motility · 2021Review
- Cellular functions of actin- and microtubule-associated septins.Current biology : CB · 2021Review
- Matrix degradation and cell proliferation are coupled to promote invasion and escape from an engineered human breast microtumor.Integrative biology : quantitative biosciences from nano to macro · 2021Article
- The Potential Anticancer Activity of Phytoconstituents against Gastric Cancer-A Review on In Vitro, In Vivo, and Clinical Studies.International journal of molecular sciences · 2020Review
- ECM Stiffness Controls the Activation and Contractility of Corneal Keratocytes in Response to TGF-β1.Biophysical journal · 2020Article
- Mechanoactivation of NOX2-generated ROS elicits persistent TRPM8 CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Soft Microenvironments Induce Chemoresistance by Increasing Autophagy Downstream of Integrin-Linked Kinase.Cancer research · 2020Article
- Regulation of mechanotransduction: Emerging roles for septins.Cytoskeleton (Hoboken, N.J.) · 2019Review
- The dualistic origin of human tumors.Seminars in cancer biology · 2018Review
- Berberine Attenuated Proliferation, Invasion and Migration by Targeting the AMPK/HNF4α/WNT5A Pathway in Gastric Carcinoma.Frontiers in pharmacology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Multinucleation is found in more than one third of tumors and is linked to increased tolerance for mutation, resistance to chemotherapy, and invasive potential. The integrity of the genome depends on proper execution of the cell cycle, which can be altered through mechanotransduction pathways as the tumor microenvironment stiffens during tumorigenesis. Here, we show that signaling downstream of matrix metalloproteinase-3 (MMP3) or TGFβ, known inducers of epithelial-mesenchymal transition (EMT), also promotes multinucleation in stiff microenvironments through Snail-dependent expression of the filament-forming protein septin-6, resulting in midbody persistence, abscission failure, and multinucleation. Consistently, we observed elevated expression of Snail and septin-6 as well as multinucleation in a human patient sample of metaplastic carcinoma of the breast, a rare classification characterized by deposition of collagen fibers and active EMT. In contrast, a soft microenvironment protected mammary epithelial cells from becoming multinucleated by preventing Snail-induced upregulation of septin-6. Our data suggest that tissue stiffening during tumorigenesis synergizes with oncogenic signaling to promote genomic abnormalities that drive cancer progression.
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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.