ArticleCancer research2015
Constitutive activation of myosin-dependent contractility sensitizes glioma tumor-initiating cells to mechanical inputs and reduces tissue invasion.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
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Who cites it
65 citing papers in PubMed, 95 citations in OpenAlex.
- Actin, connexin-43 and GAP-43 expression in gliomas: real-world associations with IDH status, tumor burden and survival.Journal of neuro-oncology · 2026Article
- The Size of Glioblastoma Spheroids Influences Patterns of Invasion and Temozolomide Efficacy.Tissue engineering. Part C, Methods · 2026Article
- Mechanotransduction in glioma stem cell fate determination: from niche mechanics to therapeutic vulnerability and state plasticity.Frontiers in cell and developmental biology · 2026Review
- Polycystin-1 Orchestrates Tumor Context-Dependent Mechanotransduction Programs Driving Epithelial-to-Mesenchymal Transition and Invasion in Solid Cancers.International journal of biological sciences · 2026Article
- Mechanical Signaling: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Size-dependent invasion and therapeutic phenotype of 42MGBA glioblastoma spheroids.bioRxiv : the preprint server for biology · 2025Article
- Article
- Intercellular contractile force attenuates chemosensitivity through Notch-MVP-mediated nuclear drug export.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ROCK2 Downregulation in Pediatric Medulloblastoma Increases Migration and Predicts the Involvement of SHH Non-canonical Signaling.The Yale journal of biology and medicine · 2025Article
- Heterogeneous focal adhesion cytoskeleton nanoarchitectures from microengineered interfacial curvature to oversee nuclear remodeling and mechanotransduction of mesenchymal stem cells.Cellular & molecular biology letters · 2025Article
- Kinase activities in pancreatic ductal adenocarcinoma with prognostic and therapeutic avenues.Molecular oncology · 2024Article
- Mechanical Constraints in Tumor Guide Emergent Spatial Patterns of Glioblastoma Cancer Stem Cells.Mechanobiology in medicine · 2024Article
- Biophysics in tumor growth and progression: from single mechano-sensitive molecules to mechanomedicine.Oncogene · 2023Review
- The study of an anoikis-related signature to predict glioma prognosis and immune infiltration.Journal of cancer research and clinical oncology · 2023Article
- Article
- Cell contractility drives mechanical memory of oral squamous cell carcinoma.Molecular biology of the cell · 2023Article
- The Mechanics of Tumor Cells Dictate Malignancy via Cytoskeleton-Mediated APC/Wnt/β-Catenin Signaling.Research (Washington, D.C.) · 2023Article
- Biomimetic Hydrogels in the Study of Cancer Mechanobiology: Overview, Biomedical Applications, and Future Perspectives.Gels (Basel, Switzerland) · 2022Review
- PNJ scaffolds promote microenvironmental regulation of glioblastoma stem-like cell enrichment and radioresistance.Biomaterials science · 2022Article
- Mechanotransduction: Exploring New Therapeutic Avenues in Central Nervous System Pathology.Frontiers in neuroscience · 2022Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Tumor-initiating cells (TIC) perpetuate tumor growth, enable therapeutic resistance, and drive initiation of successive tumors. Virtually nothing is known about the role of mechanotransductive signaling in controlling TIC tumorigenesis, despite the recognized importance of altered mechanics in tissue dysplasia and the common observation that extracellular matrix (ECM) stiffness strongly regulates cell behavior. To address this open question, we cultured primary human glioblastoma (GBM) TICs on laminin-functionalized ECMs spanning a range of stiffnesses. Surprisingly, we found that these cells were largely insensitive to ECM stiffness cues, evading the inhibition of spreading, migration, and proliferation typically imposed by compliant ECMs. We hypothesized that this insensitivity may result from insufficient generation of myosin-dependent contractile force. Indeed, we found that both pharmacologic and genetic activation of cell contractility through RhoA GTPase, Rho-associated kinase, or myosin light chain kinase restored stiffness-dependent spreading and motility, with TICs adopting the expected rounded and nonmotile phenotype on soft ECMs. Moreover, constitutive activation of RhoA restricted three-dimensional invasion in both spheroid implantation and Transwell paradigms. Orthotopic xenotransplantation studies revealed that control TICs formed tumors with classical GBM histopathology including diffuse infiltration and secondary foci, whereas TICs expressing a constitutively active mutant of RhoA produced circumscribed masses and yielded a 30% enhancement in mean survival time. This is the first direct evidence that manipulation of mechanotransductive signaling can alter the tumor-initiating capacity of GBM TICs, supporting further exploration of these signals as potential therapeutic targets and predictors of tumor-initiating capacity within heterogeneous tumor cell populations.
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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.