The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Tensional homeostasis and the malignant phenotype
Open accessAbstract
Tumors are stiffer than normal tissue, and tumors have altered integrins. Because integrins are mechanotransducers that regulate cell fate, we asked whether tissue stiffness could promote malignant behavior by modulating integrins. We found that tumors are rigid because they have a stiff stroma and elevated Rho-dependent cytoskeletal tension that drives focal adhesions, disrupts adherens junctions, perturbs tissue polarity, enhances growth, and hinders lumen formation. Matrix stiffness perturbs epithelial morphogenesis by clustering integrins to enhance ERK activation and increase ROCK-generated contractility and focal adhesions. Contractile, EGF-transformed epithelia with elevated ERK and Rho activity could be phenotypically reverted to tissues lacking focal adhesions if Rho-generated contractility or ERK activity was decreased. Thus, ERK and Rho constitute part of an integrated mechanoregulatory circuit linking matrix stiffness to cytoskeletal tension through integrins to regulate tissue phenotype.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Increased tissue stiffness triggers prosurvival and proproliferation signalling in cancer cells99.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [99]
Citations
Cites
Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion
Yeung, T., Georges, P. C., Flanagan, L. A., Marg, B., Ortiz, M., Funaki, M., Zahir, N., Ming, W., Weaver, V., & Janmey, P. A. (2005) · Cell Motility and the Cytoskeleton · doi:10.1002/cm.20041 · Cited by 2,325
Self-citationMyotubes differentiate optimally on substrates with tissue-like stiffness
Engler, A. J., Griffin, M. A., Sen, S., Bönnemann, C. G., Sweeney, H. L., & Discher, D. E. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200405004 · Cited by 1,743
Cancer cells compress intratumour vessels
Padera, T. P., Stoll, B. R., Tooredman, J. B., Capen, D., Tomaso, E. D., & Jain, R. K. (2004) · Nature · doi:10.1038/427695a · Cited by 857
Flagged first, then by citations
Research works printed but not linked: 48
- Akiri, 2003, Lysyl oxidase-related protein-1 promotes tumor fibrosis and tumor progression in vivo, Cancer Res., 63, 1657
- Arias-Salgado, 2003, Src kinase activation by direct interaction with the integrin β cytoplasmic domain, Proc. Natl. Acad. Sci. USA, 100, 13298, 10.1073/pnas.2336149100 · DOI
- Azar, 2001, A deformable finite element model of the breast for predicting mechanical deformations under external perturbations, Acad. Radiol., 8, 965, 10.1016/S1076-6332(03)80640-2 · DOI
- Beil, 2003, Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells, Nat. Cell Biol., 5, 803, 10.1038/ncb1037 · DOI
- Bershadsky, 2003, Adhesion-dependent cell mechanosensitivity, Annu. Rev. Cell Dev. Biol., 19, 677, 10.1146/annurev.cellbio.19.111301.153011 · DOI
- Burridge, 2004, Rho and Rac take center stage, Cell, 116, 167, 10.1016/S0092-8674(04)00003-0 · DOI
- Chrzanowska-Wodnicka, 1996, Rho-stimulated contractility drives the formation of stress fibers and focal adhesions, J. Cell Biol., 133, 1403, 10.1083/jcb.133.6.1403 · DOI
- Colpaert, 2001, The presence of a fibrotic focus is an independent predictor of early metastasis in lymph node-negative breast cancer patients, Am. J. Surg. Pathol., 25, 1557, 10.1097/00000478-200112000-00016 · DOI
- Croft, 2004, Conditional ROCK activation in vivo induces tumor cell dissemination and angiogenesis, Cancer Res., 64, 8994, 10.1158/0008-5472.CAN-04-2052 · DOI
- Debnath, 2003, Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures, Methods, 30, 256, 10.1016/S1046-2023(03)00032-X · DOI
- Delcommenne, 1995, Control of integrin expression by extracellular matrix, J. Biol. Chem., 270, 26794, 10.1074/jbc.270.45.26794 · DOI
- Fritz, 1999, Rho GTPases are over-expressed in human tumors, Int. J. Cancer, 81, 682, 10.1002/(SICI)1097-0215(19990531)81:5<682::AID-IJC2>3.0.CO;2-B · DOI
- Galbraith, 2002, The relationship between force and focal complex development, J. Cell Biol., 159, 695, 10.1083/jcb.200204153 · DOI · Paper page
- Gefen, 2003, Age-dependent changes in material properties of the brain and braincase of the rat, J. Neurotrauma, 20, 1163, 10.1089/089771503770802853 · DOI
- Guo, 2004, Integrin signalling during tumour progression, Nat. Rev. Mol. Cell Biol., 5, 816, 10.1038/nrm1490 · DOI
- Huang, 2004, Cell mechanics and mechanotransduction: pathways, probes, and physiology, Am. J. Physiol. Cell Physiol., 287, 1, 10.1152/ajpcell.00559.2003 · DOI
- Keller, 2003, How we are shaped: the biomechanics of gastrulation, Differentiation, 71, 171, 10.1046/j.1432-0436.2003.710301.x · DOI
- Khaled, 2004, Palpation imaging using a haptic system for virtual reality applications in medicine, Stud. Health Technol. Inform., 98, 147
- Lark, A.L., Livasy, C.A., Dressler, L., Moore, D.T., Millikan, R.C., Geradts, J., Iacocca, M., Cowan, D., Little, D., Craven, R.J., and Cance, W. (2005). High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype. Mod Pathol., in press. Published online April 29, 2005. 10.1038/modpathol.3800424. · DOI
- Lee, 2004, Mitogenic signal transduction by integrin- and growth factor receptor-mediated pathways, Mol. Cells, 17, 188, 10.1016/S1016-8478(23)13026-3 · DOI
- Li, 2003, Activation of integrin αIIbβ3 by modulation of transmembrane helix associations, Science, 300, 795, 10.1126/science.1079441 · DOI
- Liu, 2004, Polarity and proliferation are controlled by distinct signaling pathways downstream of PI3-kinase in breast epithelial tumor cells, J. Cell Biol., 164, 603, 10.1083/jcb.200306090 · DOI
- Lo, 2000, Cell movement is guided by the rigidity of the substrate, Biophys. J., 79, 144, 10.1016/S0006-3495(00)76279-5 · DOI · Paper page
- Luo, 2004, Locking the β3 integrin I-like domain into high and low affinity conformations with disulfides, J. Biol. Chem., 279, 10215, 10.1074/jbc.M312732200 · DOI
- Luo, 2005, Disrupting integrin transmembrane domain heterodimerization increases ligand binding affinity, not valency or clustering, Proc. Natl. Acad. Sci. USA, 102, 3679, 10.1073/pnas.0409440102 · DOI
- McLean, 2004, Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression, Genes Dev., 18, 2998, 10.1101/gad.316304 · DOI
- Moore, 2002, Control of embryonic lung branching morphogenesis by the Rho activator, cytotoxic necrotizing factor 1, J. Surg. Res., 104, 95, 10.1006/jsre.2002.6418 · DOI
- Netti, 2000, Role of extracellular matrix assembly in interstitial transport in solid tumors, Cancer Res., 60, 2497
- Nicolas, 2004, Cell mechanosensitivity controls the anisotropy of focal adhesions, Proc. Natl. Acad. Sci. USA, 101, 12520, 10.1073/pnas.0403539101 · DOI
- O’Brien, 2001, Rac1 orientates epithelial apical polarity through effects on basolateral laminin assembly, Nat. Cell Biol., 3, 831, 10.1038/ncb0901-831 · DOI
- O’Brien, 2002, Opinion: Building epithelial architecture: insights from three-dimensional culture models, Nat. Rev. Mol. Cell Biol., 3, 531, 10.1038/nrm859 · DOI · Paper page
- Paszek, 2004, The tension mounts: mechanics meets morphogenesis and malignancy, J. Mammary Gland Biol. Neoplasia, 9, 325, 10.1007/s10911-004-1404-x · DOI
- Reinhart-King, 2003, Endothelial cell traction forces on RGD-derivatized polyacrylamide substrata, Langmuir, 19, 1573, 10.1021/la026142j · DOI
- Riveline, 2001, Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism, J. Cell Biol., 153, 1175, 10.1083/jcb.153.6.1175 · DOI
- Roovers, 2003, Effects of rho kinase and actin stress fibers on sustained extracellular signal-regulated kinase activity and activation of G(1) phase cyclin-dependent kinases, Mol. Cell. Biol., 23, 4283, 10.1128/MCB.23.12.4283-4294.2003 · DOI
- Sahai, 2002, ROCK and Dia have opposing effects on adherens junctions downstream of Rho, Nat. Cell Biol., 4, 408, 10.1038/ncb796 · DOI
- Sahai, 2001, Cross-talk between Ras and Rho signalling pathways in transformation favours proliferation and increased motility, EMBO J., 20, 755, 10.1093/emboj/20.4.755 · DOI
- Shi, 2003, A novel mode for integrin-mediated signaling: tethering is required for phosphorylation of FAK Y397, Mol. Biol. Cell, 14, 4306, 10.1091/mbc.E03-01-0046 · DOI
- Tzima, 2001, Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment, EMBO J., 20, 4639, 10.1093/emboj/20.17.4639 · DOI
- Vial, 2003, ERK-MAPK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility, Cancer Cell, 4, 67, 10.1016/S1535-6108(03)00162-4 · DOI
- Wang, 1998, Reciprocal interactions between β1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: a different perspective in epithelial biology, Proc. Natl. Acad. Sci. USA, 95, 14821, 10.1073/pnas.95.25.14821 · DOI · Paper page
- Wang, 2000, Substrate flexibility regulates growth and apoptosis of normal but not transformed cells, Am. J. Physiol. Cell Physiol., 279, C1345, 10.1152/ajpcell.2000.279.5.C1345 · DOI
- Weaver, 2002, β4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium, Cancer Cell, 2, 205, 10.1016/S1535-6108(02)00125-3 · DOI
- White, 2004, Targeted disruption of β1-integrin in a transgenic mouse model of human breast cancer reveals an essential role in mammary tumor induction, Cancer Cell, 6, 159, 10.1016/j.ccr.2004.06.025 · DOI · Paper page
- Wozniak, 2003, ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix, J. Cell Biol., 163, 583, 10.1083/jcb.200305010 · DOI
- Zahir, 2003, Autocrine laminin-5 ligates α6β4 integrin and activates RAC and NFκB to mediate anchorage-independent survival of mammary tumors, J. Cell Biol., 163, 1397, 10.1083/jcb.200302023 · DOI
- Zajaczkowski, 2003, Cell-matrix adhesions on poly(vinyl alcohol) hydrogels, Tissue Eng., 9, 525, 10.1089/107632703322066705 · DOI
- Zhong, 1997, Rho-stimulated contractility contributes to the fibroblastic phenotype of Ras-transformed epithelial cells, Mol. Biol. Cell, 8, 2329, 10.1091/mbc.8.11.2329 · DOI
Cited by
Sorted by citations
Items 401–500 of 1,121
Cruz‐Acuña, R., Kariuki, S. W., Sugiura, K., Karaiskos, S., Plaster, E. M., Loebel, C., Efe, G., Karakasheva, T. A., Gabre, J. T., Hu, J., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci168146 · Cited by 37
“Interestingly, when we embedded cells in “stiffer” NorHA to promote protumorigenic behavior in normal cells in previous in vitro studies (38, 39) and compare favorably with measurements of human tumor stiffness (G ′ ≥ 1,000 Pa) (38, 40–42).”
Characterization of Breast Cancer Aggressiveness by Cell Mechanics
Zbiral, B., Weber, A., Vivanco, M. D., & Toca-Herrera, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512208 · Cited by 28
“Research shows that breast epithelial cells cultured in ECMs of physiological stiffness retain their normal phenotype but display structural and transcriptional hallmarks associated with tumorigenicity when cultured in ECMs of a stiffness resembling tumour stroma [24].”
BackgroundThe Effects of αvβ3 Integrin Blockage in Breast Tumor and Endothelial Cells under Hypoxia In Vitro
Casali, B. C., Gozzer, L. T., Baptista, M. P., Altei, W. F., & Selistre-de-Araújo, H. S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031745 · Cited by 33
“During tumor development, cancer cells induce collagen deposition in the surrounding microenvironment, increasing ECM stiffness, known as tumor fibrosis [5,6].”
BackgroundCurrent Status of Breast Organoid Models
Mohan, S. C., Lee, T.-Y., Giuliano, A. E., & Cui, X. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.745943 · Cited by 39
Ko, P., Choi, J., Song, S., Keum, S., Jeong, J., Hwang, Y. E., Kim, J. W., & Rhee, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116018 · Cited by 36
“For example, cancer cells cultured on a stiff matrix showed increased cytoskeletal tension, resulting in enhanced cell–ECM adhesion, disruption of cell–cell junctions, and increased cell proliferation, compared to those of cells cultured on a soft matrix [3].”
BackgroundMitchell, C. N. C., Islam, M. S., Afrin, S., Brennan, J. T., Psoter, K. J., & Segars, J. H. (2021) · Fertility and Sterility · doi:10.1016/j.fertnstert.2020.12.011 · Cited by 36
Scavo, M., Rizzi, F., Depalo, N., Fanizza, E., Ingrosso, C., Curri, M., & Giannelli, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186705 · Cited by 28
“During the carcinogenesis, the involved tissues were demonstrated to acquire rigidity compared to the normal tissues, due to an increase of cellular vimentin expression [13,14] and of cancer cell malignancy due to the re-organization of cell polarity [12,13].”
BackgroundTang, K., Zheng, Y., Hu, G., Xin, Y., Li, K., Zhang, C., Chen, X., Zhang, B., Li, X., Hu, B., et al. (2025) · Science Advances · doi:10.1126/sciadv.adq2881 · Cited by 28
“Cells can perceive mechanical milieu through integrin-mediated mechanotransduction ( 12 , 13 ), which may further regulate HDAC3 activity and cellular functions.”
Using Biosensors to Study Organoids, Spheroids and Organs-on-a-Chip: A Mechanobiology Perspective
Yousafzai, M. S., & Hammer, J. A. (2023) · Biosensors · doi:10.3390/bios13100905 · Cited by 30
“For example, tumors are typically stiffer than the surrounding healthy tissues [16].”
BackgroundSpatial and Temporal Control of 3D Hydrogel Viscoelasticity through Phototuning
Crandell, P., & Stowers, R. S. (2023) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.3c01099 · Cited by 28
Advances in mechanical biomarkers
Eroles, M., & Rico, F. (2023) · Journal of Molecular Recognition · doi:10.1002/jmr.3022 · Cited by 31
“ECM composition is known to change, stiffening the tumor microenvironment (known as fibrosis).(38,39,133,134) Studies showed that stiffening of the ECM facilitates metastases, tumoral angiogenesis,(135,136) malignancy of cancerous cells,(134,137) and correlates with aggressiveness and immune cell infiltration.”
BackgroundLuo, D., Zeng, X.-L., Zhang, S.-L., Li, D., Cheng, Z.-M., Wang, Y., Long, J.-H., Hu, Z.-Q., Long, S., Zhou, J., et al. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17673 · Cited by 27
The Study of the Extracellular Matrix in Chronic Inflammation: A Way to Prevent Cancer Initiation?
Marangio, A., Biccari, A., D’Angelo, E., Sensi, F., Spolverato, G., Pucciarelli, S., & Agostini, M. (2022) · Cancers · doi:10.3390/cancers14235903 · Cited by 34
“As it turns out, the elasticity of ECM (which can range from soft and compliant to stiff and rigid) helps to coordinate how a cell senses and perceives external forces and stimuli [38,39], providing major environmental cues that affect cell behavior [40,41].”
BackgroundThe interplay between physical cues and mechanosensitive ion channels in cancer metastasis
Bera, K., Kiepas, A., Zhang, Y., Sun, S. X., & Κωνσταντόπουλος, Κ. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.954099 · Cited by 33
“Aberrant changes in ECM structure and organization can perturb tissue homeostasis by promoting abnormal cell proliferation, elevated contractility, and transformation due to transcriptional changes (Wozniak et al., 2003; Paszek et al., 2005; Ondeck et al., 2019; Stowers et al., 2019).”
BackgroundWang, J., Xu, W., Qian, J., Wang, Y., Hou, G., & Suo, A. (2021) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2021.112159 · Cited by 29
Engineering strategies to capture the biological and biophysical tumor microenvironment in vitro
Tan, M. L., Lu, L., & Fischbach, C. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113852 · Cited by 31
Hydrogels to engineer tumor microenvironments in vitro
Fernando, K., Kwang, L. G., Lim, J. T. C., & Fong, E. L. S. (2021) · Biomaterials Science · doi:10.1039/d0bm01943g · Cited by 44
Distinct phenotypes of cancer cells on tissue matrix gel
Ruud, K. F., Hiscox, W. C., Yu, I., Chen, R. K., & Li, W. (2020) · Breast Cancer Research · doi:10.1186/s13058-020-01321-7 · Cited by 33
Cheung, B. C. H., Chen, X., Davis, H. J., Nordmann, C. S., Toth, J. M., Hodgson, L., Segall, J. E., Shenoy, V. B., & Wu, M. (2024) · Matrix Biology · doi:10.1016/j.matbio.2024.11.004 · Cited by 33
Multicellular tumor spheroids: A convenient in vitro model for translational cancer research
Patel, T. C., & Jain, N. D. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.123184 · Cited by 34
Trnkova, L., Buociková, V., Mego, M., Čumová, A., Buríková, M., Boháč, M., Miklikova, S., Cihova, M., & Smolková, B. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116559 · Cited by 29
Alaimo, A., Genovesi, S., Annesi, N., Felice, D. D., Subedi, S., Macchia, A., Manna, F. L., Ciani, Y., Vannuccini, F., Mugoni, V., et al. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00040-5 · Cited by 28
“Increasing matrix stiffness promotes tumor progression through mechano-signals (Paszek et al, 2005; Provenzano et al, 2009; Mammoto et al, 2009; Calvo et al, 2013; Panciera et al, 2017), while concurrently suppressing tumor progression by mechanically limiting the spread of tumor cells…”
Lingard, E., Dong, S., Hoyle, A., Appleton, E., Hales, A., Skaria, E., Lawless, C., Taylor-Hearn, I., Saadati, S., Chu, Q., et al. (2023) · bioRxiv · doi:10.1101/2023.09.15.557894 · Cited by 26
“SAPHs are simple, well defined and reproducible, making them amenable to a variety of modifications [21, 22].”
BackgroundCharacterizing viscoelastic properties of human melanoma tissue using Prony series
Park, S., Chien, A., Brown, I. D., & Chen, J. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1162880 · Cited by 26
“, stiffness or Young’s modulus) of many solid tumors, such as mammary (Paszek et al., 2005; Wang and Larin, 2013; Hajjarian et al., 2021), glioblastoma (Miroshnikova et al.”
BackgroundHebisch, M., Klostermeier, S., Wolf, K., Boccaccini, A. R., Wolf, S. E., Tanzi, R. E., & Kim, D. Y. (2023) · Advanced Science · doi:10.1002/advs.202205037 · Cited by 31
Cancer as a biophysical disease: Targeting the mechanical-adaptability program
Nguyen, L. T. S., Jacob, M. A. C., Parajón, E., & Robinson, D. N. (2022) · Biophysical Journal · doi:10.1016/j.bpj.2022.04.039 · Cited by 32
“Previous studies found a positive correlation between increased tissue stiffness and cancer behavior, which suggests that cancer progression depends on tumor tissue stiff-ening (53,54).”
BackgroundConfigurational fingerprints of multicellular living systems
Yang, H., Pegoraro, A. F., Han, Y., Tang, W., Abeyaratne, R., Bi, D., & Guo, M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2109168118 · Cited by 24
Extracellular Matrix for Myocardial Repair
Dziki, J. L., & Badylak, S. F. (2018) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-97421-7_8 · Cited by 25
Mechanosensitive genomic enhancers potentiate the cellular response to matrix stiffness
Cosgrove, B. D., Bounds, L. R., Taylor, C. K., Su, A. L., Rizzo, A. J., Barrera, A., Sun, T., Safi, A., Song, L., Whitlow, T. J., et al. (2025) · Science · doi:10.1126/science.adl1988 · Cited by 43
Feeling the force from within – new tools and insights into nuclear mechanotransduction
Morival, J. L. P., Hazelwood, A., & Lammerding, J. (2025) · Journal of Cell Science · doi:10.1242/jcs.263615 · Cited by 26
Shu, J., Deng, H., Zhang, Y., Wu, F., & He, J. (2024) · Regenerative Biomaterials · doi:10.1093/rb/rbae016 · Cited by 29
Durotaxis and negative durotaxis: where should cells go?
Ji, C., & Huang, Y. (2023) · Communications Biology · doi:10.1038/s42003-023-05554-y · Cited by 30
Mechanobiology in oncology: basic concepts and clinical prospects
Chen, M. B., Javanmardi, Y., Shahreza, S., Serwinski, B., Aref, A. R., Djordjevic, B., & Moeendarbary, E. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1239749 · Cited by 29
“For mammary tissues, cancerous tissue displays a signi fi cantly higher stiffness of around 4 kPa, in stark contrast to the ~0.2 kPa stiffness found in normal mammary tissue (Paszek et al., 2005).”
BackgroundInfluentialCell contractility drives mechanical memory of oral squamous cell carcinoma
Moon, S. Y., de Campos, P. S., Matte, B. F., Placone, J. K., Zanella, V. G., Martins, M. D., Lamers, M. L., & Engler, A. J. (2023) · Molecular Biology of the Cell · doi:10.1091/mbc.e22-07-0266 · Cited by 35
“These dynamic interactions can even enhance tumor growth, survival, and invasion (Geiger et al. , 2001; Paszek et al. , 2005; Butcher et al. , 2009).”
BackgroundKai, F., Ou, G., Tourdot, R. W., Stashko, C., Gaietta, G. M., Swift, M. F., Volkmann, N., Long, A. F., Han, Y., Huang, H. H., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2021109205 · Cited by 26
Self-citationCytoskeletal dynamics regulates stromal invasion behavior of distinct liver cancer subtypes
Nguyen, R. Y., Xiao, H., Gong, X., Arroyo, A., Cabral, A. T., Fischer, T. T., Flores, K., Zhang, X.-C., Robert, M., Ehrlich, B., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03121-5 · Cited by 25
Hellinger, J. W., Schömel, F., Buse, J., Lenz, C., Bauerschmitz, G., Emons, G., & Gründker, C. (2020) · Scientific Reports · doi:10.1038/s41598-020-74838-8 · Cited by 25
Valente, K., Suleman, A., & Brolo, A. (2020) · ACS Applied Bio Materials · doi:10.1021/acsabm.0c00872 · Cited by 25
Vitamin C: A stem cell promoter in cancer metastasis and immunotherapy
Fu, J., Wu, Z., Liu, J., & Wu, T. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110588 · Cited by 28
D’Angelo, E., Lindoso, R. S., Sensi, F., Pucciarelli, S., Bussolati, B., Agostini, M., & Collino, F. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01122 · Cited by 35
“In their work, they demonstrated that the substrate’s stiffness in which cells are cultivated affects epithelial morphogenesis by an integrin-mediated ERK activation and increases contractility and focal adhesions mediated by the activation of ROCK (98).”
BackgroundJokela, T. A., & LaBarge, M. A. (2021) · Current Stem Cell Reports · doi:10.1007/s40778-020-00182-2 · Cited by 24
Batasheva, S., Kotova, S., Frolova, A., & Fakhrullin, R. F. (2024) · Science and Technology of Advanced Materials · doi:10.1080/14686996.2024.2421739 · Cited by 24
Wu, W., Daneker, M., Turner, K. T., Jolley, M. A., & Lu, L. (2024) · Small Methods · doi:10.1002/smtd.202400620 · Cited by 37
IGFBP2 secretion by mammary adipocytes limits breast cancer invasion
Conway, J. R. W., Dinç, D. D., Follain, G., Paavolainen, O., Kaivola, J., Boström, P., Hartiala, P., Peuhu, E., & Ivaska, J. (2023) · Science Advances · doi:10.1126/sciadv.adg1840 · Cited by 23
“Previous studies into the role of adipocytes in breast cancer progression have primarily focused on their loss during the process ( 3 ) and the concept of increased tissue rigidity contributing to breast cancer invasion through mechanochemical signaling in cancer cells ( 36 ).”
Millet, M., Bollmann, E., Ringuette-Goulet, C., Bernard, G., Chabaud, S., Huot, M.-É., Pouliot, F., Bolduc, S., & Bordeleau, F. (2022) · Cancers · doi:10.3390/cancers14153810 · Cited by 24
“Nevertheless, increased ECM stiffness can upregulate 3D migration and could certainly be what drives the cell migration [4,66].”
BackgroundNanoparticle-mediated specific elimination of soft cancer stem cells by targeting low cell stiffness
Chen, X., Fan, Y., Sun, J., Zhang, Z., Xin, Y., Li, K., Tang, K., Du, P., Liu, Y., Wang, G., et al. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.08.053 · Cited by 26
Zerbib, E., Arif, T., Shteinfer‐Kuzmine, A., Caspi, V. C., & Shoshan‐Barmatz, V. (2021) · Cancers · doi:10.3390/cancers13112850 · Cited by 27
“In addition, conditions affecting the TME, such as hypoxia [30], acidosis [31], and tensile stress [10], exert critical influences on cancer cells.”
BackgroundOrt, C., Chen, Y., Ghagre, A., Ehrlicher, A. J., & Moraes, C. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.1c00129 · Cited by 32
The migration of metastatic breast cancer cells is regulated by matrix stiffness via YAP signalling
Chen, W., Park, S., Patel, C., Bai, Y.-X., Henary, K., Raha, A., Mohammadi, S., You, L., & Geng, F. (2021) · Heliyon · doi:10.1016/j.heliyon.2021.e06252 · Cited by 24
Esophageal Microenvironment: From Precursor Microenvironment to Premetastatic Niche
Han, P., Cao, P., Hu, S., Kong, K., Deng, Y., Zhao, B., & Li, F. (2020) · Cancer Management and Research · doi:10.2147/cmar.s258215 · Cited by 25
Biomechanical properties of laminins and their impact on cancer progression
Nonnast, E., Mira, E., & Mañes, S. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2024.189181 · Cited by 25
The emerging promise of tumour mechanobiology in cancer treatment
Papavassiliou, K. A., Basdra, E. K., & Papavassiliou, A. G. (2023) · European Journal of Cancer · doi:10.1016/j.ejca.2023.112938 · Cited by 23
Applicability of atomic force microscopy to determine cancer-related changes in cells
Lekka, M. (2022) · Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences · doi:10.1098/rsta.2021.0346 · Cited by 24
“This is linked with the internal structure of cells and tissues that changes dynamically during the organism development, functioning and, also, during disease progression [3,4].”
BackgroundBetriu, N., Andreeva, A. Y., & Semino, C. E. (2021) · Cancers · doi:10.3390/cancers13184504 · Cited by 27
“Increased matrix stiffness is a hallmark of many cancers such as breast [24], colorectal [25] and pancreatic [26] cancers.”
BackgroundRabie, E., Zhang, S. X., Dunn, C., & Nelson, C. (2021) · Molecular Biology of the Cell · doi:10.1091/mbc.e21-02-0072 · Cited by 23
“Consistent with our findings in cells cultured on plastic (Figure 1M), we found that depleting septin-6 in β 1 V737N -expressing cells reduces but does not completely prevent MNC induced by TGF β signaling (Figure 7G), indicating that septin-6 is not solely responsible for the phenotype we observe in cells undergoing…”
InfluentialAntibody-Functionalized Nanowires: A Tuner for the Activation of T Cells
Bhingardive, V., Kossover, A., Iraqi, M., Khand, B., Saux, G. L., Porgador, A., & Schvartzman, M. (2021) · Nano Letters · doi:10.1021/acs.nanolett.1c00245 · Cited by 24
External cues to drive B cell function towards immunotherapy
Stoycheva, D., Şimşek, H., Weber, W., Hauser, A. E., & Klotzsch, E. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.02.026 · Cited by 25
Panzetta, V., Verde, G. L., Pugliese, M., Artiola, V., Arrichiello, C., Muto, P., Commara, M. L., Netti, P., & Fusco, S. (2020) · Cancers · doi:10.3390/cancers12051170 · Cited by 23
“At the same time, malignant cells exhibit a very high level of focal adhesion kinase (FAK) [44], a nonreceptor tyrosine kinase activated by integrin clustering and involved in the process of disassembly of focal adhesion, and the overexpression and activation of FAK are promoted by the stiffening of the ECM [45].”
BackgroundBhattarai, S., Mackeyev, Y., Venkatesulu, B. P., Krishnan, S., & Singh, P. K. (2021) · Nanoscale · doi:10.1039/d1nr05385j · Cited by 22
Jiang, C., Centonze, A., Song, Y., Chrisnandy, A., Tika, E., Rezakhani, S., Zahedi, Z., Bouvencourt, G., Dubois, C., Keymeulen, A. V., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54843-5 · Cited by 31
“These stiffness values approximate the mechanical properties of normal mammary gland stroma (0.1 kPa) and tumor (4kPa) 34 , as well as collagen I gel at varying concentrations (2mg/ml, 0.5kPa; 4 mg/ml, 0.9kPa; 8 mg/ml, 3.3 kPa, Advanced Biomatrix).”
InfluentialEpithelial–Mesenchymal Transition Induced in Cancer Cells by Adhesion to Type I Collagen
Fujisaki, H., & Futaki, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010198 · Cited by 22
“When fibrotic tissue becomes stiffer than normal tissue [52], the increased stiffness of the cell adhesion scaffold alone induces EMT [53].”
BackgroundDevelopment of a CAFs-related gene signature to predict survival and drug response in bladder cancer
Zhang, Z., Liang, Z.-J., Li, D., Wang, L.-P., Chen, Y., Liang, Y., Jiao, W., & Niu, H. (2022) · Human Cell · doi:10.1007/s13577-022-00673-w · Cited by 22
“Changes in ECM remodeling have been shown to affect the migration of infiltrating leukocytes, which has an impact on tumor immune surveillance [23, 24].”
BackgroundLoria, R., Laquintana, V., Scalera, S., Fraioli, R., Caprara, V., Falcone, I., Bazzichetto, C., Martile, M. D., Rosanò, L., Bufalo, D. D., et al. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02354-w · Cited by 26
“A very first response of cancer cells to stimuli from tumor microenvironment is represented by actin cytoskeleton remodeling to promote survival, migration, and metastatization [34, 35].”
BackgroundActivation of Fibroblasts in Skin Cancer
Hove, L. V., & Hoste, E. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2021.09.010 · Cited by 25
Emerging technologies provide insights on cancer extracellular matrix biology and therapeutics
Cruz‐Acuña, R., Vunjak‐Novakovic, G., Burdick, J. A., & Rustgi, A. K. (2021) · iScience · doi:10.1016/j.isci.2021.102475 · Cited by 26
Kumai, J., Sasagawa, S., Horie, M., & Yui, Y. (2021) · Frontiers in Materials · doi:10.3389/fmats.2021.637278 · Cited by 28
“In cancer biology, a relationship has been demonstrated between mammary tissue stiffness and breast cancer progression (Paszek and Weaver, 2004; Paszek et al., 2005; Levental et al., 2007, 2009; Butcher et al., 2009).”
BackgroundKilinc, A. N., Han, S., Barrett, L. A., Anandasivam, N., & Nelson, C. (2021) · Molecular Biology of the Cell · doi:10.1091/mbc.e20-02-0092 · Cited by 22
“For example, the extracellular matrix (ECM) is stiffer within breast tumors than within the surrounding normal mammary tissue, which correlates with poor survival (Paszek et al., 2005).”
BackgroundLiu, S., Chen, G., Chen, Z., Wang, F., & Lv, Y. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.146485 · Cited by 21
Habeeb, I. F., Alao, T. E., Delgado, D., & Buffone, A. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1487306 · Cited by 16
Nakanishi, T., Koma, Y., Miyako, S., Torigoe, R., Yokoo, H., Omori, M., Yamanaka, K., Ishihara, N., Tsukamoto, S., Kodama, T., et al. (2024) · Cells · doi:10.3390/cells13201733 · Cited by 22
“CAFs remodel the extracellular matrix (ECM), leading to tissue stiffening, which induces signaling that promotes cancer cell survival and growth [5].”
BackgroundExploiting Matrix Stiffness to Overcome Drug Resistance
Aydın, H. B., Özçelikkale, A., & Acar, A. (2024) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.4c00445 · Cited by 23
Xiao, C., Xie, N., Shu, Q., Liang, X., Wang, Z., Wu, J., Shi, N., Huang, X., Wei, Z., Gao, X., et al. (2024) · Small · doi:10.1002/smll.202309907 · Cited by 21
Kumar, V., Naqvi, S. M., Verbruggen, A. S. K., McEvoy, E., & McNamara, L. M. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114043 · Cited by 25
Filipe, E. C., Velayuthar, S., Philp, A. M., Nobis, M., Latham, S. L., Parker, A. L., Murphy, K. J., Wyllie, K., Major, G. S., Contreras, O., et al. (2024) · Advanced Science · doi:10.1002/advs.202307963 · Cited by 26
CAFs vs. TECs: when blood feuds fuel cancer progression, dissemination and therapeutic resistance
Coursier, D., & Calvo, F. (2024) · Cellular Oncology · doi:10.1007/s13402-024-00931-z · Cited by 23
“This includes orienting fibers to promote cancer cell motil - ity, creating permissive tracks facilitating cancer cell invasion, and augmenting tissue stiffness, promoting malignant phenotypes in cancer cells [15–17].”
BackgroundCell Shape and Forces in Elastic and Structured Environments: From Single Cells to Organoids
Link, R., Weißenbruch, K., Tanaka, M., Bastmeyer, M., & Schwarz, U. S. (2023) · Advanced Functional Materials · doi:10.1002/adfm.202302145 · Cited by 25
Bond, K., Chiba, T., Wynne, K. J., Vary, C., Sims‐Lucas, S., Coburn, J. M., & Oxburgh, L. H. (2021) · Cancers · doi:10.3390/cancers13235873 · Cited by 38
“In addition to providing the substrate for cancer cell attachment, ECM determines rigidity, which profoundly influences tumor malignancy [13].”
BackgroundDirecting Multicellular Organization by Varying the Aspect Ratio of Soft Hydrogel Microwells
Pahapale, G. J., Tao, J., Nikolić, M., Gao, S. Y., Scarcelli, G., Sun, S. X., Romer, L. H., & Gracias, D. H. (2022) · Advanced Science · doi:10.1002/advs.202104649 · Cited by 30
“Studies have shown that only soft hydrogels with a stiffness less than 2 kPa support the spontaneous reorganization of epithelial cell aggregates to form lumenized structures like ducts (8, 28).”
BackgroundMapping mechanical properties of the tumor microenvironment by laser speckle rheological microscopy
Hajjarian, Z., Brachtel, E., Tshikudi, D., & Nadkarni, S. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-3898 · Cited by 21
“Furthermore, our finding that tumor stroma is significantly stiffer versus epithelium across all grades is supported by the well-established concept of the desmoplastic reaction (2).”
BackgroundPancreatic Ductal Adenocarcinoma: Relating Biomechanics and Prognosis
Curtain, B. M. M., Quirke, N., Thorpe, S. D., & Gallagher, T. K. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10122711 · Cited by 30
“Indeed, the physical properties of the tumour and stroma have been shown to be several magnitudes stiffer than healthy pancreatic tissue [22], and there is a well-documented link between stromal stiffness and cancer progression [23,24].”
BackgroundNanowire Based Mechanostimulating Platform for Tunable Activation of Natural Killer Cells
Bhingardive, V., Edri, A., Kossover, A., Saux, G. L., Khand, B., Radinsky, O., Iraqi, M., Porgador, A., & Schvartzman, M. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202103063 · Cited by 24
Curtis, K. J., Schiavi, J., Garrigle, M. J. M., Kumar, V., McNamara, L. M., & Niebur, G. L. (2020) · Journal of The Royal Society Interface · doi:10.1098/rsif.2020.0568 · Cited by 27
“20 kPa in collagen hydrogels [20], while spheroid”
BackgroundLiver epithelial focal adhesion kinase modulates fibrogenesis and hedgehog signaling
Weng, Y., Lieberthal, T. J., Zhou, V. X., Lopez-Ichikawa, M. A., Armas‐Phan, M., Bond, T. K., Yoshida, M., Choi, W., & Chang, T. T. (2020) · JCI Insight · doi:10.1172/jci.insight.141217 · Cited by 22
“Stiffened tumor stroma activates FAK and downstream cell contractility, which cooperate with growth-factor-mediated signals to potentiate proliferation and invasive behavior of malignant cells (7, 8).”
Emerging Role of Syndecans in Extracellular Matrix Remodeling in Cancer
Jang, B., Kim, A., Hwang, J., Song, H.-K., Kim, Y., & Oh, E. (2020) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155420930112 · Cited by 29
Collagen-Laponite Nanoclay Hydrogels for Tumor Spheroid Growth
Alamán‐Díez, P., Borau, C., Guerrero, P. E., Amaveda, H., Mora, M., Fraile, J. M., García‐Gareta, E., García‐Aznar, J. M., & Pérez, M. Á. (2023) · Biomacromolecules · doi:10.1021/acs.biomac.3c00257 · Cited by 25
Challenges and Opportunities Modeling the Dynamic Tumor Matrisome
Peyton, S. R., Platt, M. O., & Cukierman, E. (2023) · BME Frontiers · doi:10.34133/bmef.0006 · Cited by 24
Cell size and actin architecture determine force generation in optogenetically activated cells
Andersen, T., Wörthmüller, D., Probst, D., Wang, I., Moreau, P., Fitzpatrick, V., Boudou, T., Schwarz, U., & Balland, M. (2023) · Biophysical Journal · doi:10.1016/j.bpj.2023.01.011 · Cited by 20
“In particular, changes in RhoA regulation have been connected to the progression of cancer (24,25).”
BackgroundCamacho-Gómez, D., García‐Aznar, J. M., & Gómez‐Benito, M. J. (2022) · Engineering With Computers · doi:10.1007/s00366-022-01654-1 · Cited by 19
“To evaluate the predictive capacity of the model, we replicate the experiment developed by [35], who studied the influence of matrix rigidity in the lumen formed by MCF10A cells and concluded that matrix stiffening compromises tissue organization, inhibits lumen formation and enhances growth.”
BackgroundMethodResultInfluentialOrigin of Cancer: Cell work is the Key to Understanding Cancer Initiation and Progression
Hanselmann, R. G., & Welter, C. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.787995 · Cited by 31
Bidirectional Mechanical Response Between Cells and Their Microenvironment
Mierke, C. T. (2021) · Frontiers in Physics · doi:10.3389/fphy.2021.749830 · Cited by 36
Sato, K., Parag‐Sharma, K., Terajima, M., Musicant, A. M., Murphy, R. M., Ramsey, M. R., Hibi, H., Yamauchi, M., & Amelio, A. L. (2021) · Neoplasia · doi:10.1016/j.neo.2021.05.014 · Cited by 28
Modeling the tumor immune microenvironment for drug discovery using 3D culture
Lee, J. Y., & Chaudhuri, O. (2021) · APL Bioengineering · doi:10.1063/5.0030693 · Cited by 22
Effect of Acoustic Radiation Force on the Distribution of Nanoparticles in Solid Tumors
Afadzi, M., Myhre, O. F., Yemane, P. T., Bjørkøy, A., TORP, S. H., van Wamel, A. J. E. T., Lélu, S., Angelsen, B., & Davies, C. D. L. (2020) · IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control · doi:10.1109/tuffc.2020.3027072 · Cited by 28
“and structure of the tumor ECM [57]–[59] and the high Fig.”
Allen, S. C., Widman, J. A., Datta, A., & Suggs, L. J. (2020) · Integrative Biology · doi:10.1093/intbio/zyaa012 · Cited by 22
Nuclear envelope proteins, mechanotransduction, and their contribution to breast cancer progression
Henretta, S., & Lammerding, J. (2025) · npj Biological Physics and Mechanics · doi:10.1038/s44341-025-00018-2 · Cited by 19
“First, changes in the physical microenvironment, such as stiffening of the stromal environment, can drive pathogenic mechanoresponses that promote a pro-invasive cellular phenotype, even in normal mammary epithelial cells, as demonstrated in a landmark study two decades ago 74 .”
Progress in the mechanical properties of nanoparticles for tumor-targeting delivery
Li, Z., Xiao, C., Yang, X., & Li, Z. (2025) · Chemical Society Reviews · doi:10.1039/d3cs00912b · Cited by 35
Focal adhesion kinase regulates tendon cell mechanoresponse and physiological tendon development
Leahy, T. P., Chenna, S. S., Soslowsky, L. J., & Dyment, N. A. (2024) · The FASEB Journal · doi:10.1096/fj.202400151r · Cited by 16
Direct and cell-mediated EV-ECM interplay
Smirnova, O., Efremov, Y. M., Klyucherev, T. O., Peshkova, M., Senkovenko, A. M., Svistunov, A. А., & Timashev, P. S. (2024) · Acta Biomaterialia · doi:10.1016/j.actbio.2024.07.029 · Cited by 20
Tension directs cancer cell migration over fiber alignment through energy minimization
Zanotelli, M. R., Miller, J. P., Wang, W., Ortiz, I., Tahon, E., Bordeleau, F., & Reinhart‐King, C. A. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122682 · Cited by 16
Self-citationDiversity of Intercellular Communication Modes: A Cancer Biology Perspective
Ebrahim, T., Ebrahim, A. S., & Kandouz, M. (2024) · Cells · doi:10.3390/cells13060495 · Cited by 25
“Cancer progression is associated with defects in mechanotransduction, associated with the ECM, focal adhesions (FAs) and cytoskeletal tensions [289–291].”
Background
Metadata
- Authors
- Paszek, M. J., Zahir, N., Johnson, K. R., Lakins, J. N., Rozenberg, G. I., Gefen, A., Reinhart-King, C. A., Margulies, S. S., Dembo, M., Boettiger, D., Hammer, D. A., & Weaver, V. M.
- Affiliations
- University of Pennsylvania (US)
- Tel Aviv University (IL)
- Boston University (US)
- Corresponding author
- Weaver, Valerie M.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2005-09
- Volume
- 8
- Issue
- 3
- Pages
- 241-254
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2099052265
- Cited by
- 3,941
- References
- 0
- Citations by year
- 2026: 142 · 2025: 165 · 2024: 155 · 2023: 172 · 2022: 193 · 2021: 221 · 2020: 273 · 2019: 217 · 2018: 262 · 2017: 256 · 2016: 239 · 2015: 249 · 2014: 225 · 2013: 237 · 2012: 183
- FWCI
- 33.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministerio de Economía y Competitividad
- National Heart, Lung, and Blood Institute (R01HL057204, HL-57204, HL64388-01A1, T32HL007954, T32HL00795404)
- National Cancer Institute (R01CA078731, CA078731)
- National Institute of General Medical Sciences (R01GM057388, GM57388)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- tumor stiffness, extracellular matrix stiffness, integrins, mechanotransduction, cytoskeletal tension, Rho GTPase signaling, ERK activation, focal adhesions, adherens junctions, tissue polarity, epithelial morphogenesis, tumor stroma, contractility, malignant phenotype
- MeSH terms
- Animals, Cytoskeleton, Homeostasis, Neoplasms, Phenotype, Stress, Mechanical, 3T3 Cells, Stromal Cells, Cell Line, Tumor, Cell Shape, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
