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.
Integrity signals
Registry
Cites
Statistics
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?
Increased tissue stiffness triggers prosurvival and proproliferation signalling in cancer cells.
“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]
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 · see citing works
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 · see citing works
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 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Matrix elasticity directs stem cell lineage specification
Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006) · Cell · doi:10.1016/j.cell.2006.06.044 · Cited by 13,915 · see citing works
Remodelling the extracellular matrix in development and disease
Bonnans, C., Chou, J., & Werb, Z. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3904 · Cited by 4,367 · see citing works
The extracellular matrix at a glance
Frantz, C., Stewart, K. M., & Weaver, V. M. (2010) · Journal of Cell Science · doi:10.1242/jcs.023820 · Cited by 4,334 · see citing works
Self-citationMatrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
Levental, K. R., Yu, H., Kass, L., Lakins, J. N., Egeblad, M., Erler, J. T., Fong, S. F. T., Csiszar, K., Giaccia, A., Weninger, W., et al. (2009) · Cell · doi:10.1016/j.cell.2009.10.027 · Cited by 4,101 · see citing works
Self-citationA framework for advancing our understanding of cancer-associated fibroblasts
Sahai, E., Astsaturov, I., Cukierman, E., DeNardo, D. G., Egeblad, M., Evans, R. M., Fearon, D., Greten, F. R., Hingorani, S. R., Hunter, T., et al. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0238-1 · Cited by 3,863 · see citing works
Self-citationThe extracellular matrix: A dynamic niche in cancer progression
Lu, P., Weaver, V. M., & Werb, Z. (2012) · Journal of Cell Biology · doi:10.1083/jcb.201102147 · Cited by 3,024 · see citing works
Self-citationHydrogels with tunable stress relaxation regulate stem cell fate and activity
Chaudhuri, O., Gu, L., Klumpers, D., Darnell, M., Bencherif, S. A., Weaver, J. C., Huebsch, N., Lee, H.-P., Lippens, E., Duda, G. N., et al. (2016) · Nature Materials · doi:10.1038/nmat4489 · Cited by 2,443 · see citing works
Local force and geometry sensing regulate cell functions
Vogel, V., & Sheetz, M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1890 · Cited by 2,328 · see citing works
Extracellular Matrix Degradation and Remodeling in Development and Disease
Lu, P., Takai, K., Weaver, V. M., & Werb, Z. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005058 · Cited by 2,265 · see citing works
Self-citationDeconstructing the third dimension – how 3D culture microenvironments alter cellular cues
Baker, B. M., & Chen, C. S. (2012) · Journal of Cell Science · doi:10.1242/jcs.079509 · Cited by 1,760 · see citing works
Lab-on-Skin: A Review of Flexible and Stretchable Electronics for Wearable Health Monitoring
Liu, Y., Pharr, M., & Salvatore, G. A. (2017) · ACS Nano · doi:10.1021/acsnano.7b04898 · Cited by 1,725 · see citing works
Aragona, M., Panciera, T., Manfrin, A., Giulitti, S., Michielin, F., Elvassore, N., Dupont, S., & Piccolo, S. (2013) · Cell · doi:10.1016/j.cell.2013.07.042 · Cited by 1,651 · see citing works
Signaling mechanisms of the epithelial-mesenchymal transition
Gonzalez, D. M., & Medici, D. (2014) · Science Signaling · doi:10.1126/scisignal.2005189 · Cited by 1,721 · see citing works
Formation and function of the myofibroblast during tissue repair
Hinz, B. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700613 · Cited by 1,658 · see citing works
Cellular mechanotransduction: putting all the pieces together again
Ingber, D. E. (2006) · The FASEB Journal · doi:10.1096/fj.05-5424rev · Cited by 1,627 · see citing works
Hypoxia and the extracellular matrix: drivers of tumour metastasis
Gilkes, D. M., Semenza, G. L., & Wirtz, D. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3726 · Cited by 1,520 · see citing works
Every step of the way: integrins in cancer progression and metastasis
Hamidi, H., & Ivaska, J. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0038-z · Cited by 1,493 · see citing works
Calvo, F., Ege, N., Grande-Garcia, A., Hooper, S., Jenkins, R. P., Chaudhry, S. I., Harrington, K., Williamson, P., Moeendarbary, E., Charras, G., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2756 · Cited by 1,478 · see citing works
Jaalouk, D. E., & Lammerding, J. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2597 · Cited by 1,396 · see citing works
Biomechanics and biophysics of cancer cells☆
SURESH, S. (2007) · Acta Biomaterialia · doi:10.1016/j.actbio.2007.04.002 · Cited by 1,284 · see citing works
Erler, J. T., Bennewith, K. L., Cox, T. R., Lang, G., Bird, D., Koong, A., Le, Q.-T., & Giaccia, A. J. (2009) · Cancer Cell · doi:10.1016/j.ccr.2008.11.012 · Cited by 1,231 · see citing works
Mechanical regulation of cell function with geometrically modulated elastomeric substrates
Fu, J., Wang, Y.-K., Yang, M. T., Desai, R. A., Yu, X., Liu, Z., & Chen, C. S. (2010) · Nature Methods · doi:10.1038/nmeth.1487 · Cited by 1,073 · see citing works
The Role of Mechanical Forces in Tumor Growth and Therapy
Jain, R. K., Martin, J. D., & Stylianopoulos, T. (2014) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071813-105259 · Cited by 1,044 · see citing works
Transduction of mechanical and cytoskeletal cues by YAP and TAZ
Halder, G., Dupont, S., & Piccolo, S. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3416 · Cited by 985 · see citing works
Extracellular matrix and its therapeutic potential for cancer treatment
Huang, J., Zhang, L., Wan, D., Zhou, L., Zheng, S., Lin, S., & Qiao, Y. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00544-0 · Cited by 962 · see citing works
TGFβ biology in cancer progression and immunotherapy
Derynck, R., Turley, S. J., & Akhurst, R. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0403-1 · Cited by 944 · see citing works
Three-dimensional culture systems in cancer research: Focus on tumor spheroid model
Nath, S., & Devi, G. R. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.03.013 · Cited by 919 · see citing works
Elosegui-Artola, A., Oria, R., Chen, Y., Kosmalska, A., Pérez-González, C., Castro, N., Zhu, C., Trepat, X., & Roca-Cusachs, P. (2016) · Nature Cell Biology · doi:10.1038/ncb3336 · Cited by 858 · see citing works
Chaudhuri, O., Koshy, S. T., Branco da Cunha, C., Shin, J.-W., Verbeke, C. S., Allison, K. H., & Mooney, D. J. (2014) · Nature Materials · doi:10.1038/nmat4009 · Cited by 820 · see citing works
Three-Dimensional Cell Cultures in Drug Discovery and Development
Fang, Y., & Eglen, R. M. (2017) · SLAS Discovery · doi:10.1177/1087057117696795 · Cited by 849 · see citing works
The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer
Affo, S., Yu, L.-X., & Schwabe, R. F. (2017) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-052016-100322 · Cited by 757 · see citing works
Mechanobiology of collective cell behaviours
Ladoux, B., & Mège, R.-M. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.98 · Cited by 749 · see citing works
Cell–extracellular matrix mechanotransduction in 3D
Saraswathibhatla, A., Indana, D., & Chaudhuri, O. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00583-1 · Cited by 859 · see citing works
Nia, H. T., Munn, L. L., & Jain, R. K. (2020) · Science · doi:10.1126/science.aaz0868 · Cited by 865 · see citing works
“Today, there are numerous studies showing how thematerial properties—in particular, the stiffness of themicroenvironment—are central to many traits of cancer (79), including proliferation (80, 81), angiogenesis (82), metabolism (83), invasion (84–86), andmigration andmetastasis (87–89) (Fig.”
BackgroundSchrader, J., Gordon-Walker, T. T., Aucott, R. L., van Deemter, M., Quaas, A., Walsh, S., Benten, D., Forbes, S. J., Wells, R. G., & Iredale, J. P. (2011) · Hepatology · doi:10.1002/hep.24108 · Cited by 720 · see citing works
The cancer glycocalyx mechanically primes integrin-mediated growth and survival
Paszek, M. J., DuFort, C. C., Rossier, O., Bainer, R., Mouw, J. K., Godula, K., Hudak, J. E., Lakins, J. N., Wijekoon, A. C., Cassereau, L., et al. (2014) · Nature · doi:10.1038/nature13535 · Cited by 699 · see citing works
Self-citationThree-dimensional organotypic culture: experimental models of mammalian biology and disease
Shamir, E. R., & Ewald, A. J. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3873 · Cited by 719 · see citing works
Mechanical compression drives cancer cells toward invasive phenotype
Tse, J. M., Cheng, G., Tyrrell, J. A., Wilcox-Adelman, S. A., Boucher, Y., Jain, R. K., & Munn, L. L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1118910109 · Cited by 631 · see citing works
The extracellular matrix in tumor progression and metastasis
Eble, J. A., & Niland, S. (2019) · Clinical & Experimental Metastasis · doi:10.1007/s10585-019-09966-1 · Cited by 613 · see citing works
Collagen as a double-edged sword in tumor progression
Fang, M., Yuan, J., Peng, C., & Li, Y. (2014) · Tumor Biology · doi:10.1007/s13277-013-1511-7 · Cited by 580 · see citing works
Loessner, D., Stok, K. S., Lutolf, M. P., Hutmacher, D. W., Clements, J. A., & Rizzi, S. C. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.07.064 · Cited by 602 · see citing works
Hirata, E., Girotti, M. R., Viros, A., Hooper, S., Spencer-Dene, B., Matsuda, M., Larkin, J., Marais, R., & Sahai, E. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.008 · Cited by 593 · see citing works
Mechanoreciprocity in cell migration
van Helvert, S., Storm, C., & Friedl, P. (2018) · Nature Cell Biology · doi:10.1038/s41556-017-0012-0 · Cited by 587 · see citing works
LOX-Mediated Collagen Crosslinking Is Responsible for Fibrosis-Enhanced Metastasis
Cox, T. R., Bird, D., Baker, A.-M., Barker, H. E., Ho, M. W.-Y., Lang, G., & Erler, J. T. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-2233 · Cited by 571 · see citing works
Chen, Y., Kim, J., Yang, S., Wang, H., Wu, C.-J., Sugimoto, H., LeBleu, V. S., & Kalluri, R. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.02.007 · Cited by 566 · see citing works
Lampi, M. C., & Reinhart-King, C. A. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aao0475 · Cited by 551 · see citing works
Self-citationLymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity
Swartz, M. A., & Lund, A. W. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3186 · Cited by 544 · see citing works
The obese adipose tissue microenvironment in cancer development and progression
Quail, D. F., & Dannenberg, A. J. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0126-x · Cited by 542 · see citing works
A history of exploring cancer in context
Maman, S., & Witz, I. P. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0006-7 · Cited by 502 · see citing works
Dagdeviren, C., Shi, Y., Joe, P., Ghaffari, R., Balooch, G., Usgaonkar, K., Gur, O., Tran, P. L., Crosby, J. R., Meyer, M., et al. (2015) · Nature Materials · doi:10.1038/nmat4289 · Cited by 513 · see citing works
The extracellular matrix in breast cancer
Insua-Rodríguez, J., & Oskarsson, T. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.12.017 · Cited by 470 · see citing works
Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression
Niland, S., Riscanevo, A. X., & Eble, J. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010146 · Cited by 528 · see citing works
Cancer-Associated Fibroblasts Build and Secure the Tumor Microenvironment
Liu, T., Zhou, L., Li, D., Andl, T., & Zhang, Y. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00060 · Cited by 446 · see citing works
The central role of muscle stem cells in regenerative failure with aging
Blau, H. M., Cosgrove, B. D., & Ho, A. T. V. (2015) · Nature Medicine · doi:10.1038/nm.3918 · Cited by 437 · see citing works
Role of YAP/TAZ in cell-matrix adhesion-mediated signalling and mechanotransduction
Dupont, S. (2016) · Experimental Cell Research · doi:10.1016/j.yexcr.2015.10.034 · Cited by 449 · see citing works
3D collagen alignment limits protrusions to enhance breast cancer cell persistence
Riching, K. M., Cox, B. L., Salick, M. R., Pehlke, C., Riching, A. S., Ponik, S. M., Bass, B. R., Crone, W. C., Jiang, Y., Weaver, A. M., et al. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2014.10.035 · Cited by 446 · see citing works
Age-related vascular stiffening: causes and consequences
Kohn, J. C., Lampi, M. C., & Reinhart-King, C. A. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00112 · Cited by 440 · see citing works
Self-citationChallenges of applying multicellular tumor spheroids in preclinical phase
Han, S. J., Kwon, S., & Kim, K. S. (2021) · Cancer Cell International · doi:10.1186/s12935-021-01853-8 · Cited by 428 · see citing works
Tumor Microenvironment and Differential Responses to Therapy
Hirata, E., & Sahai, E. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026781 · Cited by 422 · see citing works
A novel 3D mammalian cell perfusion-culture system in microfluidic channels
Toh, Y.-C., Zhang, C., Zhang, J., Khong, Y. M., Chang, S., Samper, V. D., van Noort, D., Hutmacher, D. W., & Yu, H. (2007) · Lab on a Chip · doi:10.1039/b614872g · Cited by 414 · see citing works
Biomaterials and emerging anticancer therapeutics: engineering the microenvironment
Gu, L., & Mooney, D. J. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.3 · Cited by 407 · see citing works
Hinz, B. (2009) · Current Rheumatology Reports · doi:10.1007/s11926-009-0017-1 · Cited by 373 · see citing works
A Pericellular Collagenase Directs the 3-Dimensional Development of White Adipose Tissue
Chun, T.-H., Hotary, K. B., Sabeh, F., Saltiel, A. R., Allen, E. D., & Weiss, S. J. (2006) · Cell · doi:10.1016/j.cell.2006.02.050 · Cited by 378 · see citing works
Sleeboom, J. J. F., van Tienderen, G. S., Schenke‐Layland, K., van der Laan, L. J. W., Khalil, A., & Verstegen, M. M. A. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adg3840 · Cited by 391 · see citing works
Fibrous nonlinear elasticity enables positive mechanical feedback between cells and ECMs
Hall, M. S., Alisafaei, F., Ban, E., Feng, X., Hui, C.-Y., Shenoy, V. B., & Wu, M. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1613058113 · Cited by 360 · see citing works
Viscoelastic hydrogels for 3D cell culture
Chaudhuri, O. (2017) · Biomaterials Science · doi:10.1039/c7bm00261k · Cited by 353 · see citing works
Synthetic Materials in the Study of Cell Response to Substrate Rigidity
Nemir, S., & West, J. L. (2010) · Annals of Biomedical Engineering · doi:10.1007/s10439-009-9811-1 · Cited by 318 · see citing works
Engineering cancer microenvironments for in vitro 3-D tumor models
Asghar, W., El Assal, R., Shafiee, H., Pitteri, S., Paulmurugan, R., & Demirci, U. (2015) · Materials Today · doi:10.1016/j.mattod.2015.05.002 · Cited by 316 · see citing works
The elastic modulus of Matrigel™ as determined by atomic force microscopy
Soofi, S. S., Last, J. A., Liliensiek, S. J., Nealey, P. F., & Murphy, C. J. (2009) · Journal of Structural Biology · doi:10.1016/j.jsb.2009.05.005 · Cited by 309 · see citing works
Tharp, K. M., Kersten, K., Maller, O., Timblin, G. A., Stashko, C., Canale, F. P., Menjivar, R. E., Hayward, M.-K., Berestjuk, I., ten Hoeve, J., et al. (2024) · Nature Cancer · doi:10.1038/s43018-024-00775-4 · Cited by 304 · see citing works
“We hypothesized that either TAMs in stiff and fibrotic tumors may engage an autocrine TGFβ1 signaling circuit or that stiffness potentiates TGFβ signaling, as other growth factor signaling circuits are mechanosensitive 31 .”
Self-citationShen, Y., Wang, X., Lu, J., Salfenmoser, M., Wirsik, N. M., Schleußner, N., Imle, A., Valls, A. F., Radhakrishnan, P., Liang, J., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.05.005 · Cited by 337 · see citing works
Controlling the biodistribution and clearance of nanomedicines
Cabral, H., Li, J., Miyata, K., & Kataoka, K. (2023) · Nature Reviews Bioengineering · doi:10.1038/s44222-023-00138-1 · Cited by 303 · see citing works
“…CAFs) and acellular (ECM) components of the stroma 234,235 ; for example, during tumour progression, CAFs overproduce ECM proteins (collagen I, elastin, fibronectin and hyaluronan), secrete growth factors and modify the tumour tissue through contractile forces, thereby building up stress 236,237 .”
RETRACTED: Collagen Prolyl Hydroxylases Are Essential for Breast Cancer Metastasis
Gilkes, D. M., Chaturvedi, P., Bajpai, S., Wong, C. C., Wei, H., Pitcairn, S., Hubbi, M. E., Wirtz, D., & Semenza, G. L. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3963 · Cited by 296 · see citing works
RetractedMechanoregulation of YAP and TAZ in Cellular Homeostasis and Disease Progression
Cai, X., Wang, K.-C., & Meng, Z. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.673599 · Cited by 311 · see citing works
Microfluidic platforms for mechanobiology
Polacheck, W. J., Li, R., Uzel, S. G. M., & Kamm, R. D. (2013) · Lab on a Chip · doi:10.1039/c3lc41393d · Cited by 272 · see citing works
Engineering and physical sciences in oncology: challenges and opportunities
Mitchell, M. J., Jain, R. K., & Langer, R. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.83 · Cited by 273 · see citing works
Extracellular matrix stiffness: Mechanisms in tumor progression and therapeutic potential in cancer
Zhang, M., & Zhang, B. (2025) · Experimental Hematology & Oncology · doi:10.1186/s40164-025-00647-2 · Cited by 269 · see citing works
“For example, breast cancer tissue (5–10 kPa) is stiffer than normal breast tissue (800 Pa) [9].”
Matrix viscoelasticity controls spatiotemporal tissue organization
Elósegui-Artola, A., Gupta, A., Najibi, A. J., Seo, B. R., Garry, R., Tringides, C. M., de Lázaro, I., Darnell, M., Gu, W., Zhou, Q., et al. (2022) · Nature Materials · doi:10.1038/s41563-022-01400-4 · Cited by 293 · see citing works
Sodek, K. L., Ringuette, M. J., & Brown, T. J. (2009) · International Journal of Cancer · doi:10.1002/ijc.24188 · Cited by 248 · see citing works
Procollagen lysyl hydroxylase 2 is essential for hypoxia-induced breast cancer metastasis
Gilkes, D. M., Bajpai, S., Wong, C. C., Chaturvedi, P., Hubbi, M. E., Wirtz, D., & Semenza, G. L. (2013) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-12-0629 · Cited by 252 · see citing works
RetractedVan De Water, L., Varney, S., & Tomasek, J. J. (2013) · Advances in Wound Care · doi:10.1089/wound.2012.0393 · Cited by 251 · see citing works
Biophysics of tumor microenvironment and cancer metastasis – a mini review
Emon, B., Bauer, J., Jain, Y., Jung, B., & Saif, T. (2018) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2018.07.003 · Cited by 245 · see citing works
Truskewycz, A., Yin, H. F., Halberg, N., Lai, D. T. H., Ball, A. S., Truong, V. K., Rybicka, A. M., & Cole, I. S. (2022) · Small · doi:10.1002/smll.202106342 · Cited by 303 · see citing works
Cancer-Associated Fibroblasts: Tumorigenicity and Targeting for Cancer Therapy
Glabman, R. A., Choyke, P. L., & Sato, N. (2022) · Cancers · doi:10.3390/cancers14163906 · Cited by 259 · see citing works
Zhang, D., Wang, G., Yu, X., Wei, T., Farbiak, L., Johnson, L. T., Taylor, A. M., Xu, J., Hong, Y., Zhu, H., et al. (2022) · Nature Nanotechnology · doi:10.1038/s41565-022-01122-3 · Cited by 243 · see citing works
Stiff matrix induces exosome secretion to promote tumour growth
Wu, B., Liu, D.-A., Guan, L., Myint, P. K., Chin, L., Dang, H., Xu, Y., Ren, J., Li, T., Yu, Z., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01092-1 · Cited by 240 · see citing works
Self-citationExtracellular matrix signaling in morphogenesis and repair
Clause, K. C., & Barker, T. H. (2013) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2013.04.011 · Cited by 230 · see citing works
Mechanosensitive systems at the cadherin–F-actin interface
Huveneers, S., & de Rooij, J. (2013) · Journal of Cell Science · doi:10.1242/jcs.109447 · Cited by 222 · see citing works
Fattet, L., Jung, H., Matsumoto, M. W., Aubol, B. E., Kumar, A., Adams, J. A., Chen, A. C., Sah, R. L., Engler, A. J., Pasquale, E. B., et al. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.05.031 · Cited by 248 · see citing works
“During tumor development, increased deposition, modification and remodeling of the ECM generate a highly fibrotic tumor microenvironment with increased matrix rigidity, which is associated with poor patient prognosis (Wei et al., 2015; Chang et al., 2013; Mujtaba et al., 2013; Lu et al., 2012; Levental et al., 2009; P…”
BackgroundMethodInfluentialFoster, C. T., Gualdrini, F., & Treisman, R. (2017) · Genes & Development · doi:10.1101/gad.304501.117 · Cited by 202 · see citing works
The Extracellular Matrix in Skin Inflammation and Infection
Pfisterer, K., Shaw, L. E., Symmank, D., & Weninger, W. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.682414 · Cited by 244 · see citing works
Grauel, A. L., Nguyen, B., Ruddy, D., Laszewski, T., Schwartz, S., Chang, J., Chen, J., Piquet, M., Pelletier, M., Yan, Z., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19920-5 · Cited by 211 · see citing works
Mechanical Adaptability of Tumor Cells in Metastasis
Gensbittel, V., Kräter, M., Harlepp, S., Busnelli, I., Guck, J. R., & Goetz, J. G. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.10.011 · Cited by 231 · see citing works
Bulle, A. S., & Lim, K. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00341-1 · Cited by 203 · see citing works
Li, X., & Wang, J. (2020) · International Journal of Biological Sciences · doi:10.7150/ijbs.44943 · Cited by 213 · see citing works
“Increasing ECM stiffness also induces malignant phenotypes, characterized by Rho-dependent cytoskeletal tension that leads to enhanced cell-ECM adhesions, disruption of cell-cell junctions and increased growth [33].”
BackgroundWallstabe, L., Göttlich, C., Nelke, L. C., Kühnemundt, J., Schwarz, T., Nerreter, T., Einsele, H., Walles, H., Dandekar, G., Nietzer, S. L., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.126345 · Cited by 193 · see citing works
Complex mechanics of the heterogeneous extracellular matrix in cancer
Malandrino, A., Mak, M., Kamm, R. D., & Moeendarbary, E. (2018) · Extreme Mechanics Letters · doi:10.1016/j.eml.2018.02.003 · Cited by 192 · see citing works
Sapudom, J., Rubner, S., Martin, S., Kurth, T., Riedel, S., Mierke, C. T., & Pompe, T. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.02.022 · Cited by 195 · see citing works
Immune Modulatory Properties of Collagen in Cancer
Rømer, A. M. A., Thorseth, M., & Madsen, D. H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.791453 · Cited by 231 · see citing works
“This in turn activates signaling pathways, increases cytoskeletal tension and further FA formation, promoting malignant transformation (53).”
BackgroundLinking cell mechanical memory and cancer metastasis
Cambria, E., Coughlin, M. F., Floryan, M. A., Offeddu, G. S., Shelton, S. E., & Kamm, R. D. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-023-00656-5 · Cited by 196 · see citing works
“…force generation by tumour cells in response to high ECM stiffness is driven by integrin clustering and signalling through EGFR, which activates extracellular signal-regulated kinase 1/2 (ERK1/2) and increases RHO–Rho-associated kinase (ROCK)- mediated actomyosin contractility 25,108 .”
Influential
- 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
