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Mechanobiology is an emerging interdisciplinary field that studies how biological mechanisms are regulated by biomechanical forces and how physical principles can be leveraged to innovate new therapeutic strategies. This article reviews state-of-the-art mechanobiology knowledge about the yes-associated protein (YAP), a key mechanosensitive protein, and its roles in the development of drug resistance in human cancer. Specifically, the article discusses three topics: how YAP is mechanically regulated in living cells; the molecular mechanobiology mechanisms by which YAP, along with other functional pathways, influences drug resistance of cancer cells (particularly lung cancer cells); and finally, how the mechanical regulation of YAP can influence drug resistance and vice versa. By integrating these topics, we present a unified framework that has the potential to bring theoretical insights into the design of novel mechanomedicines and advance next-generation cancer therapies to suppress tumor progression and metastasis.<\/jats:p>","DOI":"10.3390\/ijms241512491","type":"journal-article","created":{"date-parts":[[2023,8,6]],"date-time":"2023-08-06T10:01:53Z","timestamp":1691316113000},"page":"12491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["YAP at the Crossroads of Biomechanics and Drug Resistance in Human Cancer"],"prefix":"10.3390","volume":"24","author":[{"given":"Miao","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL 32611, USA"},{"name":"UF Health Cancer Center, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL 32611, USA"},{"name":"UF Health Cancer Center, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cole","family":"Mackey","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32603, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Physics, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Guan","sequence":"additional","affiliation":[{"name":"UF Health Cancer Center, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Physics, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8106-6663","authenticated-orcid":false,"given":"Guangrong","family":"Zheng","sequence":"additional","affiliation":[{"name":"UF Health Cancer Center, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32603, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arkaprava","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Florida, Gainesville, FL 32603, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyi","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32603, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Vulpe","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, University of Florida, Gainesville, FL 32603, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL 32611, USA"},{"name":"UF Health Cancer Center, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1126\/science.1116995","article-title":"Tissue Cells Feel and Respond to the Stiffness of Their Substrate","volume":"310","author":"Discher","year":"2005","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1126\/science.1171643","article-title":"Growth Factors, Matrices, and Forces Combine and Control Stem Cells","volume":"324","author":"Discher","year":"2009","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nrm1890","article-title":"Local Force and Geometry Sensing Regulate Cell Functions","volume":"7","author":"Vogel","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nrm2592","article-title":"Mechanotransduction in Development: A Growing Role for Contractility","volume":"10","author":"Wozniak","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nrm2594","article-title":"Mechanotransduction at a Distance: Mechanically Coupling the Extracellular Matrix with the Nucleus","volume":"10","author":"Wang","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1039\/D1SM01618K","article-title":"Towards an Integrative Understanding of Cancer Mechanobiology: Calcium, YAP, and MicroRNA under Biophysical Forces","volume":"18","author":"Liang","year":"2022","journal-title":"Soft Matter"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.actbio.2022.03.058","article-title":"Lose the Stress: Viscoelastic Materials for Cell Engineering","volume":"163","author":"Carvalho","year":"2023","journal-title":"Acta Biomater."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1039\/c0ib00095g","article-title":"Biophysical Regulation of Tumor Cell Invasion: Moving beyond Matrix Stiffness","volume":"3","author":"Pathak","year":"2011","journal-title":"Integr. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"040401","DOI":"10.1063\/5.0135299","article-title":"Mechanobiology of the Cell Nucleus","volume":"6","author":"Lammerding","year":"2022","journal-title":"APL Bioeng."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6151","DOI":"10.1039\/c0sm01453b","article-title":"How Far Cardiac Cells Can See Each Other Mechanically","volume":"7","author":"Tang","year":"2011","journal-title":"Soft Matter"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7197","DOI":"10.1039\/c2sm25533b","article-title":"A Novel Technique for Micro-Patterning Proteins and Cells on Polyacrylamide Gels","volume":"8","author":"Tang","year":"2012","journal-title":"Soft Matter"},{"key":"ref_12","first-page":"9","article-title":"YAP\/TAZ as Master Regulators in Cancer: Modulation, Function and Therapeutic Approaches","volume":"4","author":"Piccolo","year":"2022","journal-title":"Nat. Cancer"},{"key":"ref_13","first-page":"2145","article-title":"Yes-Associated Protein (YAP65) Is a Proline-Rich Phosphoprotein That Binds to the SH3 Domain of the Yes Proto-Oncogene Product","volume":"9","author":"Sudol","year":"1994","journal-title":"Oncogene"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.semcdb.2012.05.004","article-title":"The YAP and TAZ Transcription Co-Activators: Key Downstream Effectors of the Mammalian Hippo Pathway","volume":"23","author":"Hong","year":"2012","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1101\/gad.1664408","article-title":"TEAD Mediates YAP-Dependent Gene Induction and Growth Control","volume":"22","author":"Zhao","year":"2008","journal-title":"Genes. Dev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Haderk, F., Fern\u00e1ndez-M\u00e9ndez, C., \u010cech, L., Yu, J., Meraz, I.M., Olivas, V., Rabago, D.B., Lucas Kerr, D., Gomez, C., and Allegakoen, D.V. (Cancer Biol., 2021). A Focal Adhesion Kinase-YAP Signaling Axis Drives Drug Tolerant Persister Cells and Residual Disease in Lung Cancer, Cancer Biol., preprint.","DOI":"10.1101\/2021.10.23.465573"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1016\/j.febslet.2014.04.012","article-title":"YAP\/TAZ as Mechanosensors and Mechanotransducers in Regulating Organ Size and Tumor Growth","volume":"588","author":"Low","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1101\/gad.1602907","article-title":"Inactivation of YAP Oncoprotein by the Hippo Pathway Is Involved in Cell Contact Inhibition and Tissue Growth Control","volume":"21","author":"Zhao","year":"2007","journal-title":"Genes. Dev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.ccell.2016.05.005","article-title":"YAP\/TAZ at the Roots of Cancer","volume":"29","author":"Zanconato","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.devcel.2019.06.003","article-title":"The Hippo Signaling Pathway in Development and Disease","volume":"50","author":"Zheng","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"28976","DOI":"10.18632\/oncotarget.6721","article-title":"Functional Genomics Screen Identifies YAP1 as a Key Determinant to Enhance Treatment Sensitivity in Lung Cancer Cells","volume":"7","author":"Cheng","year":"2016","journal-title":"Oncotarget"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.cell.2013.07.042","article-title":"A Mechanical Checkpoint Controls Multicellular Growth through YAP\/TAZ Regulation by Actin-Processing Factors","volume":"154","author":"Aragona","year":"2013","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.stem.2017.03.023","article-title":"An FAK-YAP-MTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice","volume":"21","author":"Hu","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.ccell.2019.01.009","article-title":"A Platform of Synthetic Lethal Gene Interaction Networks Reveals That the GNAQ Uveal Melanoma Oncogene Controls the Hippo Pathway through FAK","volume":"35","author":"Feng","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1096\/fj.201700721R","article-title":"FAK Controls the Mechanical Activation of YAP, a Transcriptional Regulator Required for Durotaxis","volume":"32","author":"Lachowski","year":"2018","journal-title":"FASEB J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s41419-019-1664-4","article-title":"Activation of Aurora A Kinase Increases YAP Stability via Blockage of Autophagy","volume":"10","author":"Wang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/35074532","article-title":"Force and Focal Adhesion Assembly: A Close Relationship Studied Using Elastic Micropatterned Substrates","volume":"3","author":"Balaban","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1126\/science.1162912","article-title":"Stretching Single Talin Rod Molecules Activates Vinculin Binding","volume":"323","author":"Liu","year":"2009","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/j.cell.2012.11.034","article-title":"Force Fluctuations within Focal Adhesions Mediate ECM-Rigidity Sensing to Guide Directed Cell Migration","volume":"151","author":"Plotnikov","year":"2012","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/ncb3336","article-title":"Mechanical Regulation of a Molecular Clutch Defines Force Transmission and Transduction in Response to Matrix Rigidity","volume":"18","author":"Oria","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1038\/s41467-021-22602-5","article-title":"Force-FAK Signaling Coupling at Individual Focal Adhesions Coordinates Mechanosensing and Microtissue Repair","volume":"12","author":"Zhou","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13045-022-01252-0","article-title":"Targeting Extracellular Matrix Stiffness and Mechanotransducers to Improve Cancer Therapy","volume":"15","author":"Jiang","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"166555","DOI":"10.1016\/j.bbadis.2022.166555","article-title":"Mechanobiology of Solid Tumors","volume":"1868","author":"Gargalionis","year":"2022","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"165625","DOI":"10.1016\/j.bbadis.2019.165625","article-title":"Matrix Stiffness Modulates ILK-Mediated YAP Activation to Control the Drug Resistance of Breast Cancer Cells","volume":"1866","author":"Qin","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"718834","DOI":"10.3389\/fcell.2021.718834","article-title":"Substrate Stiffness Modulates the Growth, Phenotype, and Chemoresistance of Ovarian Cancer Cells","volume":"9","author":"Fan","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1002\/jcp.27078","article-title":"Cirrhotic Stiffness Affects the Migration of Hepatocellular Carcinoma Cells and Induces Sorafenib Resistance through YAP","volume":"234","author":"Gao","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"462","DOI":"10.15252\/embj.201592081","article-title":"Actin Remodeling Confers BRAF Inhibitor Resistance to Melanoma Cells through YAP \/ TAZ Activation","volume":"35","author":"Kim","year":"2016","journal-title":"EMBO J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/cas.15622","article-title":"Yes-associated protein 1 Mediates Initial Cell Survival during Lorlatinib Treatment through AKT Signaling in ROS1 -rearranged Lung Cancer","volume":"114","author":"Yamazoe","year":"2023","journal-title":"Cancer Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.ccell.2015.03.008","article-title":"Intravital Imaging Reveals How BRAF Inhibition Generates Drug-Tolerant Microenvironments with High Integrin \u03921\/FAK Signaling","volume":"27","author":"Hirata","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/978-1-0716-3271-0_7","article-title":"Functional Interrogation of Ca2+ Signals in Human Cancer Cells In Vitro and Ex Vivo by Fluorescent Microscopy and Molecular Tools","volume":"Volume 2679","author":"Revzin","year":"2023","journal-title":"Microfluidic Systems for Cancer Diagnosis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.semcancer.2022.03.012","article-title":"Chemotherapy as a Regulator of Extracellular Matrix-Cell Communication: Implications in Therapy Resistance","volume":"86","author":"Single","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1101\/gad.192856.112","article-title":"Genetic and Pharmacological Disruption of the TEAD\u2013YAP Complex Suppresses the Oncogenic Activity of YAP","volume":"26","author":"Huang","year":"2012","journal-title":"Genes. Dev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.trecan.2019.02.010","article-title":"YAP\/TAZ Signaling and Resistance to Cancer Therapy","volume":"5","author":"Nguyen","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6744","DOI":"10.1038\/s41467-022-34559-0","article-title":"Pharmacological Blockade of TEAD\u2013YAP Reveals Its Therapeutic Limitation in Cancer Cells","volume":"13","author":"Sun","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.bbrc.2016.04.089","article-title":"Hippo Pathway Effector YAP Inhibition Restores the Sensitivity of EGFR-TKI in Lung Adenocarcinoma Having Primary or Acquired EGFR-TKI Resistance","volume":"474","author":"Lee","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"110257","DOI":"10.18632\/oncotarget.22628","article-title":"Inhibition of YAP Function Overcomes BRAF Inhibitor Resistance in Melanoma Cancer Stem Cells","volume":"8","author":"Fisher","year":"2017","journal-title":"Oncotarget"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1126\/scitranslmed.aau6296","article-title":"Selective YAP\/TAZ Inhibition in Fibroblasts via Dopamine Receptor D1 Agonism Reverses Fibrosis","volume":"11","author":"Haak","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1002\/jcb.21187","article-title":"Tumor Microenvironment Abnormalities: Causes, Consequences, and Strategies to Normalize","volume":"101","author":"Fukumura","year":"2007","journal-title":"J. Cell. Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.coisb.2017.04.005","article-title":"Genome Variation across Cancers Scales with Tissue Stiffness\u2014An Invasion-Mutation Mechanism and Implications for Immune Cell Infiltration","volume":"2","author":"Pfeifer","year":"2017","journal-title":"Curr. Opin. Syst. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.coche.2016.01.011","article-title":"Mechanotransduction in Cancer","volume":"11","author":"Chin","year":"2016","journal-title":"Curr. Opin. Chem. Eng."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/ncomms1873","article-title":"Dynamic Force-Induced Direct Dissociation of Protein Complexes in a Nuclear Body in Living Cells","volume":"3","author":"Poh","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4000","DOI":"10.1038\/ncomms5000","article-title":"Generation of Organized Germ Layers from a Single Mouse Embryonic Stem Cell","volume":"5","author":"Poh","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Tang, X., Wen, Q., Kuhlenschmidt, T.B., Kuhlenschmidt, M.S., Janmey, P.A., and Saif, T.A. (2012). Attenuation of Cell Mechanosensitivity in Colon Cancer Cells during In Vitro Metastasis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050443"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1146\/annurev-physiol-021317-121245","article-title":"Steps in Mechanotransduction Pathways That Control Cell Morphology","volume":"81","author":"Wolfenson","year":"2019","journal-title":"Annu. Rev. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10137","article-title":"Role of YAP\/TAZ in Mechanotransduction","volume":"474","author":"Dupont","year":"2011","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1039\/C9NR09452K","article-title":"Mechanical Force Regulation of YAP by F-Actin and GPCR Revealed by Super-Resolution Imaging","volume":"12","author":"Gao","year":"2020","journal-title":"Nanoscale"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.cell.2017.10.008","article-title":"Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores","volume":"171","author":"Andreu","year":"2017","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"121823","DOI":"10.1016\/j.biomaterials.2022.121823","article-title":"Human Cancer Cells Generate Spontaneous Calcium Transients and Intercellular Waves That Modulate Tumor Growth","volume":"290","author":"Liang","year":"2022","journal-title":"Biomaterials"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/1476-4598-13-131","article-title":"A Mechanically-Induced Colon Cancer Cell Population Shows Increased Metastatic Potential","volume":"13","author":"Tang","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1016\/j.bpj.2010.08.034","article-title":"Mechanical Force Affects Expression of an In Vitro Metastasis-Like Phenotype in HCT-8 Cells","volume":"99","author":"Tang","year":"2010","journal-title":"Biophys. J."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Tang, X., Tofangchi, A., Anand, S.V., and Saif, T.A. (2014). A Novel Cell Traction Force Microscopy to Study Multi-Cellular System. PLoS Comput. Biol., 10.","DOI":"10.1371\/journal.pcbi.1003631"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Luo, Q., Zhang, J., Huang, M., Lin, G., Tanaka, M., Lepler, S., Guan, J., Siemann, D., and Tang, X. (2022). Automatic Multi-Functional Integration Program (AMFIP) towards All-Optical Mechano-Electrophysiology Interrogation. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0266098"},{"key":"ref_63","first-page":"62934","article-title":"All-Optical Mechanobiology Interrogation of Yes-Associated Protein in Human Cancer and Normal Cells Using a Multi-Functional System","volume":"178","author":"Luo","year":"2021","journal-title":"JoVE"},{"key":"ref_64","first-page":"64098","article-title":"Combining 3D Magnetic Force Actuator and Multi-Functional Fluorescence Imaging to Study Nucleus Mechanobiology","volume":"185","author":"Huang","year":"2022","journal-title":"JoVE"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"15321","DOI":"10.1038\/ncomms15321","article-title":"YAP Regulates Cell Mechanics by Controlling Focal Adhesion Assembly","volume":"8","author":"Nardone","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41563-022-01400-4","article-title":"Matrix Viscoelasticity Controls Spatiotemporal Tissue Organization","volume":"22","author":"Gupta","year":"2023","journal-title":"Nat. Mater."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.actbio.2016.06.037","article-title":"Matrix Directed Adipogenesis and Neurogenesis of Mesenchymal Stem Cells Derived from Adipose Tissue and Bone Marrow","volume":"42","author":"Lee","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.biomaterials.2015.08.005","article-title":"Geometric Guidance of Integrin Mediated Traction Stress during Stem Cell Differentiation","volume":"69","author":"Lee","year":"2015","journal-title":"Biomaterials"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1350025","DOI":"10.1142\/S1758825113500257","article-title":"Adhesivity of Colon Cancer Cells During In Vitro Metastasis","volume":"5","author":"Tang","year":"2013","journal-title":"Int. J. Appl. Mech."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s12195-010-0102-6","article-title":"Substrate Stiffness and Cell Area Predict Cellular Traction Stresses in Single Cells and Cells in Contact","volume":"3","author":"Califano","year":"2010","journal-title":"Cel. Mol. Bioeng."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Koushki, N., Ghagre, A., Srivastava, L.K., Sitaras, C., Yoshie, H., Molter, C., and Ehrlicher, A.J. (Biophysics, 2020). Lamin A Redistribution Mediated by Nuclear Deformation Determines Dynamic Localization of YAP, Biophysics, preprint.","DOI":"10.1101\/2020.03.19.998708"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6333","DOI":"10.1038\/ncomms7333","article-title":"Cyclic Stretching of Soft Substrates Induces Spreading and Growth","volume":"6","author":"Cui","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1016\/j.bpj.2015.05.010","article-title":"Cytoskeletal to Nuclear Strain Transfer Regulates YAP Signaling in Mesenchymal Stem Cells","volume":"108","author":"Driscoll","year":"2015","journal-title":"Biophys. J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"72","DOI":"10.15252\/embr.201642681","article-title":"Osmotic Stress-induced Phosphorylation by NLK at Ser128 Activates YAP","volume":"18","author":"Hong","year":"2017","journal-title":"EMBO Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.jhep.2021.05.018","article-title":"Focal Adhesion Kinase (FAK) Promotes Cholangiocarcinoma Development and Progression via YAP Activation","volume":"75","author":"Song","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1172\/JCI122440","article-title":"C-Abl Regulates YAPY357 Phosphorylation to Activate Endothelial Atherogenic Responses to Disturbed Flow","volume":"129","author":"Li","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1038\/s41556-022-00927-7","article-title":"Mechanical Force Application to the Nucleus Regulates Nucleocytoplasmic Transport","volume":"24","author":"Andreu","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1158\/0008-5472.CAN-21-3695","article-title":"Understanding Drug Sensitivity and Tackling Resistance in Cancer","volume":"82","author":"Tyner","year":"2022","journal-title":"Cancer Res."},{"key":"ref_79","first-page":"258","article-title":"Overcoming the Challenges of Cancer Drug Resistance through Bacterial-Mediated Therapy","volume":"5","author":"Zargar","year":"2019","journal-title":"Chronic Dis. Transl. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.trecan.2019.02.003","article-title":"Polytherapy and Targeted Cancer Drug Resistance","volume":"5","author":"Chatterjee","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.ymthe.2022.11.011","article-title":"PROTAC Therapy as a New Targeted Therapy for Lung Cancer","volume":"31","author":"Li","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/1-4020-3414-8_17","article-title":"Role of Tumour Microenvironment in Chemoresistance","volume":"Volume 15","author":"Meadows","year":"2005","journal-title":"Integration\/Interaction of Oncologic Growth"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nrc3599","article-title":"Cancer Drug Resistance: An Evolving Paradigm","volume":"13","author":"Holohan","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/s41598-017-18527-z","article-title":"Enhanced YAP Expression Leads to EGFR TKI Resistance in Lung Adenocarcinomas","volume":"8","author":"Lee","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"497","DOI":"10.18632\/genesandcancer.136","article-title":"NSCLC Depend upon YAP Expression and Nuclear Localization after Acquiring Resistance to EGFR Inhibitors","volume":"8","author":"McGowan","year":"2017","journal-title":"Genes Cancer"},{"key":"ref_86","first-page":"3949","article-title":"Role of YAP in Lung Cancer Resistance to Cisplatin","volume":"16","author":"Song","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/ng.3218","article-title":"The Hippo Effector YAP Promotes Resistance to RAF- and MEK-Targeted Cancer Therapies","volume":"47","author":"Lin","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.ccell.2019.12.006","article-title":"Treatment-Induced Tumor Dormancy through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway","volume":"37","author":"Kurppa","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Reinhold, W.C., Varma, S., Sousa, F., Sunshine, M., Abaan, O.D., Davis, S.R., Reinhold, S.W., Kohn, K.W., Morris, J., and Meltzer, P.S. (2014). NCI-60 Whole Exome Sequencing and Pharmacological CellMiner Analyses. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101670"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1101\/gad.189601","article-title":"The NF2 Tumor Suppressor Gene Product, Merlin, Mediates Contact Inhibition of Growth through Interactions with CD44","volume":"15","author":"Morrison","year":"2001","journal-title":"Genes Dev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6801","DOI":"10.1038\/s41388-019-0924-1","article-title":"The Hippo Pathway Modulates Resistance to BET Proteins Inhibitors in Lung Cancer Cells","volume":"38","author":"Gobbi","year":"2019","journal-title":"Oncogene"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Rozengurt, E., and Eibl, G. (2021). Crosstalk between KRAS, SRC and YAP Signaling in Pancreatic Cancer: Interactions Leading to Aggressive Disease and Drug Resistance. Cancers, 13.","DOI":"10.3390\/cancers13205126"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ccell.2014.11.006","article-title":"Paradox-Breaking RAF Inhibitors That Also Target SRC Are Effective in Drug-Resistant BRAF Mutant Melanoma","volume":"27","author":"Girotti","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Hsu, P.-C., Yang, C.-T., Jablons, D.M., and You, L. (2020). The Crosstalk between Src and Hippo\/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC). Cancers, 12.","DOI":"10.3390\/cancers12061361"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3482","DOI":"10.1158\/0008-5472.CAN-08-2524","article-title":"Connective Tissue Growth Factor Confers Drug Resistance in Breast Cancer through Concomitant Up-Regulation of Bcl-XL and CIAP1","volume":"69","author":"Wang","year":"2009","journal-title":"Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.bbamcr.2014.01.007","article-title":"CTGF Increases Drug Resistance to Paclitaxel by Upregulating Survivin Expression in Human Osteosarcoma Cells","volume":"1843","author":"Tsai","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"24015","DOI":"10.1074\/jbc.M402305200","article-title":"Cyr61 Expression Confers Resistance to Apoptosis in Breast Cancer MCF-7 Cells by a Mechanism of NF-\u039aB-Dependent XIAP Up-Regulation","volume":"279","author":"Lin","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3139","DOI":"10.1111\/jcmm.13593","article-title":"Inhibition of Yes-associated Protein Down-regulates PD-L1 (CD274) Expression in Human Malignant Pleural Mesothelioma","volume":"22","author":"Hsu","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s12032-023-01978-y","article-title":"ACADL Suppresses PD-L1 Expression to Prevent Cancer Immune Evasion by Targeting Hippo\/YAP Signaling in Lung Adenocarcinoma","volume":"40","author":"Li","year":"2023","journal-title":"Med. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.molcel.2021.01.010","article-title":"Interferon-\u03b3 Induces Tumor Resistance to Anti-PD-1 Immunotherapy by Promoting YAP Phase Separation","volume":"81","author":"Yu","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1016\/j.bbagen.2014.01.010","article-title":"Extracellular Matrix: A Dynamic Microenvironment for Stem Cell Niche","volume":"1840","author":"Gattazzo","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)\u2014General. Subj."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1097\/IJG.0000000000000108","article-title":"Biology of the Extracellular Matrix: An Overview","volume":"23","author":"Yue","year":"2014","journal-title":"J. Glaucoma"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jsamd.2021.02.009","article-title":"An Integrated Microfluidic Concentration Gradient Generator for Mechanical Stimulation and Drug Delivery","volume":"6","author":"Kashaninejad","year":"2021","journal-title":"J. Sci. Adv. Mater. Devices"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nature13701","article-title":"Piezo1 Integration of Vascular Architecture with Physiological Force","volume":"515","author":"Li","year":"2014","journal-title":"Nature"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Xin, Y., Li, K., Yang, M., and Tan, Y. (2020). Fluid Shear Stress Induces EMT of Circulating Tumor Cells via JNK Signaling in Favor of Their Survival during Hematogenous Dissemination. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218115"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3946","DOI":"10.1091\/mbc.E15-07-0456","article-title":"Microenvironment Rigidity Modulates Responses to the HER2 Receptor Tyrosine Kinase Inhibitor Lapatinib via YAP and TAZ Transcription Factors","volume":"26","author":"Lin","year":"2015","journal-title":"MBoC"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"eabb2630","DOI":"10.1126\/sciadv.abb2630","article-title":"Extracellular Matrix Stiffness Determines DNA Repair Efficiency and Cellular Sensitivity to Genotoxic Agents","volume":"6","author":"Deng","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1167\/iovs.63.1.16","article-title":"Matrix Mechanotransduction via Yes-Associated Protein in Human Lamina Cribrosa Cells in Glaucoma","volume":"63","author":"Murphy","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"5749","DOI":"10.1016\/j.biomaterials.2014.03.058","article-title":"Sorafenib Resistance and JNK Signaling in Carcinoma during Extracellular Matrix Stiffening","volume":"35","author":"Nguyen","year":"2014","journal-title":"Biomaterials"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Wang, C., Jiang, X., Huang, B., Zhou, W., Cui, X., Zheng, C., Liu, F., Bi, J., Zhang, Y., and Luo, H. (2021). Inhibition of Matrix Stiffness Relating Integrin \u03921 Signaling Pathway Inhibits Tumor Growth in Vitro and in Hepatocellular Cancer Xenografts. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08982-3"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/s41419-022-04976-6","article-title":"Ascitic Fluid Shear Stress in Concert with Hepatocyte Growth Factor Drive Stemness and Chemoresistance of Ovarian Cancer Cells via the C-Met-PI3K\/Akt-MiR-199a-3p Signaling Pathway","volume":"13","author":"Hassan","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1038\/s41467-019-09755-0","article-title":"YAP-Independent Mechanotransduction Drives Breast Cancer Progression","volume":"10","author":"Lee","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"620514","DOI":"10.3389\/fmolb.2021.620514","article-title":"The Road of Solid Tumor Survival: From Drug-Induced Endoplasmic Reticulum Stress to Drug Resistance","volume":"8","author":"Cao","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.nano.2011.09.015","article-title":"Correlative Nanomechanical Profiling with Super-Resolution F-Actin Imaging Reveals Novel Insights into Mechanisms of Cisplatin Resistance in Ovarian Cancer Cells","volume":"8","author":"Sharma","year":"2012","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_115","first-page":"2621","article-title":"The Malignancy of Metastatic Ovarian Cancer Cells Is Increased on Soft Matrices Through a Mechanosensitive Rho\u2013ROCK Pathway","volume":"127","author":"McGrail","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.bbamcr.2017.11.012","article-title":"Soft Drug-Resistant Ovarian Cancer Cells Migrate via Two Distinct Mechanisms Utilizing Myosin II-Based Contractility","volume":"1865","author":"Kapoor","year":"2018","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1093\/nar\/gkaa1202","article-title":"DNA Damage Alters Nuclear Mechanics through Chromatin Reorganization","volume":"49","author":"Cook","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"504","DOI":"10.3389\/fcell.2020.00504","article-title":"Focused Ultrasound Stimulates ER Localized Mechanosensitive PANNEXIN-1 to Mediate Intracellular Calcium Release in Invasive Cancer Cells","volume":"8","author":"Lee","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2104696","DOI":"10.1002\/advs.202104696","article-title":"Mechano-Nanoswitches for Ultrasound-Controlled Drug Activation","volume":"9","author":"Huo","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"120866","DOI":"10.1016\/j.biomaterials.2021.120866","article-title":"Selective Killing of Transformed Cells by Mechanical Stretch","volume":"275","author":"Tijore","year":"2021","journal-title":"Biomaterials"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/12491\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:26:47Z","timestamp":1760128007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/12491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,6]]},"references-count":120,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["ijms241512491"],"URL":"https:\/\/doi.org\/10.3390\/ijms241512491","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,6]]}}}