{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T06:19:02Z","timestamp":1770358742859,"version":"3.49.0"},"reference-count":70,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Repha GmbH, Langenhagen, Germany"},{"name":"Brigitta & Norbert Muth Stiftung, Wiesbaden, Germany"},{"name":"Brigitte und Dr. Konstanze Wegener-Stiftung, D\u00fcsseldorf, Germany"},{"name":"Dr. Peter und Gabriele Strohmaier-Stiftung, G\u00fctersloh, Germany"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Aggressive metastatic progression often develops in bladder cancer patients with acquired cisplatin or gemcitabine resistance. The potential of the natural isothiocyanates allyl-isothiocyanate (AITC), butyl-isothiocyanate (BITC), and phenylethyl-isothiocyanate (PEITC) to inhibit adhesion and migration of cisplatin- or gemcitabine-resistant and sensitive RT112, T24, and TCCSUP bladder cancer cell lines was investigated. Parameters determined were: cell interaction with collagen or fibronectin, chemotaxis, and membrane receptors involved in adhesion (total and activated integrins \u03b21, \u03b24, \u03b25, CD44s, and CD44v3-v7). CD44s\u2019 location and adhesion- and migration-related signaling proteins were determined. AITC blocked adhesion of almost all sensitive and resistant cancer cells. PEITC and BITC suppressed fibronectin interaction of sensitive and resistant RT112. All three isothiocyanates diminished chemotaxis in all cell lines. Integrin expression was differentially altered but CD44s and CD44v were not altered. BITC and PEITC translocated CD44s from the cell membrane to cytoplasm. The tumor suppressor E-cadherin increased, whereas focal adhesion kinase (FAK), linked to integrin signaling, was deactivated after isothiocyanate treatment. Blocking FAK, \u03b21, \u03b24, or \u03b25 was associated with reduced chemotaxis. Thus, AITC, BITC, and PEITC blocked adhesion and migration in cisplatin- and gemcitabine-resistant bladder cancer cells. This was associated with altered integrin expression and signaling, CD44s translocation, and enhanced E-cadherin.<\/jats:p>","DOI":"10.3390\/molecules31030555","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T15:24:19Z","timestamp":1770305059000},"page":"555","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Isothiocyanates Block Adhesion and Invasion of Gemcitabine- and Cisplatin-Resistant Bladder Cancer Cell Lines"],"prefix":"10.3390","volume":"31","author":[{"given":"Jochen","family":"Rutz","sequence":"first","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Grein","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"},{"name":"Department of Urology, Goethe-University, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Laqua","sequence":"additional","affiliation":[{"name":"Department of Urology, Goethe-University, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenza","family":"Benhassine","sequence":"additional","affiliation":[{"name":"Department of Urology, Goethe-University, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eren","family":"Perktas","sequence":"additional","affiliation":[{"name":"Department of Urology, Goethe-University, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jindrich","family":"Cinatl","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, Goethe-University, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix K.-H.","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Urology, Goethe-University, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Haferkamp","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-8707","authenticated-orcid":false,"given":"Eva","family":"Juengel","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5107-3523","authenticated-orcid":false,"given":"Igor","family":"Tsaur","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"},{"name":"Department of Urology, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sascha D.","family":"Markowitsch","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0129-7972","authenticated-orcid":false,"given":"Roman A.","family":"Blaheta","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany"},{"name":"Department of Urology, Goethe-University, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/ijc.35278","article-title":"The GLOBOCAN 2022 cancer estimates: Data sources, methods, and a snapshot of the cancer burden worldwide","volume":"156","author":"Filho","year":"2025","journal-title":"Int. J. Cancer"},{"key":"ref_2","unstructured":"National Cancer Institute (2025, July 21). Bladder Cancer Prognosis and Survival Rates, Available online: https:\/\/www.cancer.gov\/types\/bladder\/survival."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1111\/iju.70164","article-title":"Recent Advances and Future Directions in Bladder Preservation Therapy for Muscle-Invasive Bladder Cancer","volume":"32","author":"Kimura","year":"2025","journal-title":"Int. J. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/S0140-6736(20)30230-0","article-title":"Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): A multicentre, randomised, placebo-controlled phase 3 trial","volume":"395","author":"Galsky","year":"2020","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103972","DOI":"10.1016\/j.esmoop.2024.103972","article-title":"Atezolizumab monotherapy for metastatic urothelial carcinoma: Final analysis from the phase II IMvigor210 trial","volume":"9","author":"Rosenberg","year":"2024","journal-title":"ESMO Open"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.annonc.2022.11.012","article-title":"Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: Results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up","volume":"34","author":"Balar","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e275","DOI":"10.3747\/co.25.3884","article-title":"Complementary and alternative medicine use in patients before and after a cancer diagnosis","volume":"25","author":"Buckner","year":"2018","journal-title":"Curr. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/HNP.0000000000000665","article-title":"Complementary and Alternative Medicine Among Adult Cancer Patients: A Cross-sectional Study","volume":"39","author":"Emami","year":"2025","journal-title":"Holist. Nurs. Pract."},{"key":"ref_9","unstructured":"Aycil, \u0130., and Karaca, A. (2025). Assessment of Cancer Patients\u2019 Attitudes Toward Holistic Complementary and Alternative Medicine and Factors Influencing These Attitudes. Altern. Ther. Health Med., AT11536."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1159\/000546767","article-title":"A Current Assessment of the Use of Complementary Medicine in German Cancer Patients: The CONKO 022 Investigation","volume":"48","author":"Bleumer","year":"2025","journal-title":"Oncol. Res. Treat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.3332\/ecancer.2024.1786","article-title":"Prevalence and associated factors of herbal medicine use among breast cancer patients: A cross-sectional study in Morocco","volume":"18","author":"Baladi","year":"2024","journal-title":"Ecancermedicalscience"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sulaiman, C., George, B.P., Balachandran, I., and Abrahamse, H. (2025). Cancer and Traditional Medicine: An Integrative Approach. Pharmaceuticals, 18.","DOI":"10.3390\/ph18050644"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107107","DOI":"10.1016\/j.phrs.2024.107107","article-title":"Isothiocyanates in medicine: A comprehensive review on phenylethyl-, allyl-, and benzyl-isothiocyanates","volume":"201","author":"Hoch","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rutz, J., Maxeiner, S., Grein, T., Sonnenburg, M., Khadir, S.E., Makhatelashvili, N., Mann, J., Xie, H., Cinatl, J., and Thomas, A. (2022). Allyl-, Butyl- and Phenylethyl-Isothiocyanate Modulate Akt-mTOR and Cyclin-CDK Signaling in Gemcitabine- and Cisplatin-Resistant Bladder Cancer Cell Lines. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231910996"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"348","DOI":"10.4062\/biomolther.2022.019","article-title":"Benzyl Isothiocyanate-Induced Cytotoxicity via the Inhibition of Autophagy and Lysosomal Function in AGS Cells","volume":"30","author":"Po","year":"2022","journal-title":"Biomol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e1534","DOI":"10.1038\/cddis.2014.495","article-title":"Nuclear factor-kappaB sensitizes to benzyl isothiocyanate-induced antiproliferation in p53-deficient colorectal cancer cells","volume":"5","author":"Abe","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Cheng, N., Diao, H., Lin, Z., Gao, J., Zhao, Y., Zhang, W., Wang, Q., Lin, J., Zhang, D., and Jin, Y. (2020). Benzyl Isothiocyanate Induces Apoptosis and Inhibits Tumor Growth in Canine Mammary Carcinoma via Downregulation of the Cyclin B1\/Cdk1 Pathway. Front. Vet. Sci., 7.","DOI":"10.3389\/fvets.2020.580530"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e17532","DOI":"10.7717\/peerj.17532","article-title":"Phenethyl isothiocyanate inhibits the carcinogenic properties of hepatocellular carcinoma Huh7.5.1 cells by activating MAPK\/PI3K-Akt\/p53 signaling pathways","volume":"12","author":"Du","year":"2024","journal-title":"PeerJ"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Strusi, G., Suelzu, C.M., Weldon, S., Giffin, J., M\u00fcnsterberg, A.E., and Bao, Y. (2023). Combination of Phenethyl Isothiocyanate and Dasatinib Inhibits Hepatocellular Carcinoma Metastatic Potential through FAK\/STAT3\/Cadherin Signalling and Reduction of VEGF Secretion. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15102390"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s41401-023-01178-4","article-title":"Phenethyl isothiocyanate inhibits metastasis potential of non-small cell lung cancer cells through FTO mediated TLE1 m6A modification","volume":"45","author":"Zhang","year":"2024","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2108289","DOI":"10.1155\/2022\/2108289","article-title":"Phenethyl Isothiocyanate Suppresses the Proinflammatory Cytokines in Human Glioblastoma Cells through the PI3K\/Akt\/NF-\u03baB Signaling Pathway In Vitro","volume":"2022","author":"Hsu","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/tox.24020","article-title":"Allyl isothiocyanate induces DNA damage and inhibits DNA repair-associated proteins in a human gastric cancer cells in vitro","volume":"39","author":"Shih","year":"2024","journal-title":"Environ. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1177\/153537020623100408","article-title":"Allyl isothiocyanate and its N-acetylcysteine conjugate suppress metastasis via inhibition of invasion, migration, and matrix metalloproteinase-2\/-9 activities in SK-Hep 1 human hepatoma cells","volume":"231","author":"Hwang","year":"2006","journal-title":"Exp. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hsieh, C.C., Yang, C.Y., Peng, B., Ho, S.L., Tsao, C.H., Lin, C.K., Lin, C.S., Lin, G.J., Lin, H.Y., and Huang, H.C. (2023). Allyl Isothiocyanate Suppresses the Proliferation in Oral Squamous Cell Carcinoma via Mediating the KDM8\/CCNA1 Axis. Biomedicines, 11.","DOI":"10.3390\/biomedicines11102669"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7842","DOI":"10.1002\/fsn3.4296","article-title":"Isothiocyanates attenuate heparin-induced proliferation of colon cancer cells in vitro","volume":"12","author":"Zhang","year":"2024","journal-title":"Food Sci. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1158\/1535-7163.MCT-05-0041","article-title":"Mitochondria are the primary target in isothiocyanate-induced apoptosis in human bladder cancer cells","volume":"4","author":"Tang","year":"2005","journal-title":"Mol. Cancer Ther."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Grzywa, R., Psurski, M., Gajda, A., Gajda, T., and Janczewski, \u0141. (2023). Isothiocyanates as Tubulin Polymerization Inhibitors-Synthesis and Structure-Activity Relationship Studies. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241813674"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"19552","DOI":"10.3390\/ijms151119552","article-title":"Antimicrobial activity of isothiocyanates from cruciferous plants against methicillin-resistant Staphylococcus aureus (MRSA)","volume":"15","author":"Dias","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Xie, H., Rutz, J., Maxeiner, S., Grein, T., Thomas, A., Juengel, E., Chun, F.K., Cinatl, J., Haferkamp, A., and Tsaur, I. (2024). Sulforaphane Inhibits Adhesion and Migration of Cisplatin- and Gemcitabine-Resistant Bladder Cancer Cells In Vitro. Nutrients, 16.","DOI":"10.3390\/nu16050623"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Barboura, M., Cornebise, C., Hermetet, F., Guerrache, A., Selmi, M., Salek, A., Chekir-Ghedira, L., Aires, V., and Delmas, D. (2022). Tannic Acid, A Hydrolysable Tannin, Prevents Transforming Growth Factor-\u03b2-Induced Epithelial-Mesenchymal Transition to Counteract Colorectal Tumor Growth. Cells, 11.","DOI":"10.3390\/cells11223645"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.biopha.2018.06.110","article-title":"Effects of multi and selective targeted tyrosine kinase inhibitors on function and signaling of different bladder cancer cells","volume":"106","author":"Kessel","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/carcin\/bgr255","article-title":"The molecular basis that unifies the metabolism, cellular uptake and chemopreventive activities of dietary isothiocyanates","volume":"33","author":"Zhang","year":"2012","journal-title":"Carcinogenesis"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3164\/jcbn.17-91","article-title":"Physiological relevance of covalent protein modification by dietary isothiocyanates","volume":"62","author":"Nakamura","year":"2018","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.bcp.2012.11.017","article-title":"\u03b2-phenylethyl isothiocyanate reverses platinum resistance by a GSH-dependent mechanism in cancer cells with epithelial-mesenchymal transition phenotype","volume":"85","author":"Wu","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mahapatra, E., Sengupta, D., Kumar, R., Dehury, B., Das, S., Roy, M., and Mukherjee, S. (2022). Phenethylisothiocyanate Potentiates Platinum Therapy by Reversing Cisplatin Resistance in Cervical Cancer. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.803114"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4567","DOI":"10.21037\/jtd-24-827","article-title":"Identification of a prognostic gene signature in patients with cisplatin resistant squamous cell lung cancer","volume":"16","author":"Mu","year":"2024","journal-title":"J. Thorac. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3518","DOI":"10.1245\/s10434-018-6706-0","article-title":"Predictive Value of CD44 in Muscle-Invasive Bladder Cancer and Its Relationship with IL-6 Signaling","volume":"25","author":"Wu","year":"2018","journal-title":"Ann. Surg. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Senbanjo, L.T., and Chellaiah, M.A. (2017). CD44: A Multifunctional Cell Surface Adhesion Receptor Is a Regulator of Progression and Metastasis of Cancer Cells. Front. Cell Dev. Biol., 5.","DOI":"10.3389\/fcell.2017.00018"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Skandalis, S.S. (2023). CD44 Intracellular Domain: A Long Tale of a Short Tail. Cancers, 15.","DOI":"10.3390\/cancers15205041"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"101116","DOI":"10.1016\/j.drup.2024.101116","article-title":"A distinct subset of urothelial cells with enhanced EMT features promotes chemotherapy resistance and cancer recurrence by increasing COL4A1-ITGB1 mediated angiogenesis","volume":"76","author":"Guo","year":"2024","journal-title":"Drug Resist. Updat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"E70333","DOI":"10.1002\/mco2.70333","article-title":"Epithelial-Mesenchymal Transition in Cancer: Insights into Therapeutic Targets and Clinical Implications","volume":"6","author":"Srinivasan","year":"2025","journal-title":"MedComm"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"de Abreu Pereira, D., Sandim, V., Fernandes, T.F.B., Almeida, V.H., Rocha, M.R., do Amaral, R.J.F.C., Rossi, M.I.D., Kalume, D.E., and Zingali, R.B. (2022). Proteomic Analysis of HCC-1954 and MCF-7 Cell Lines Highlights Crosstalk between \u03b1v and \u03b21 Integrins, E-Cadherin and HER-2. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231710194"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.neo.2014.03.011","article-title":"Resistance to the mTOR inhibitor temsirolimus alters adhesion and migration behavior of renal cell carcinoma cells through an integrin \u03b15- and integrin \u03b23-dependent mechanism","volume":"16","author":"Juengel","year":"2014","journal-title":"Neoplasia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/bjc.2012.313","article-title":"Resistance to the mTOR-inhibitor RAD001 elevates integrin \u03b12- and \u03b21-triggered motility, migration and invasion of prostate cancer cells","volume":"107","author":"Tsaur","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s10120-021-01239-9","article-title":"Integrin \u03b21 orchestrates the abnormal cell-matrix attachment and invasive behaviour of E-cadherin dysfunctional cells","volume":"25","author":"Figueiredo","year":"2022","journal-title":"Gastric Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Farsinejad, S., Centeno, D., Savas-Carstens, J., Polotaye, T., Pavlovi\u010d, T., Babvey, P., Muranen, T., Miedziarek, C., Jasi\u0144ski, P., and Dziabaszewska, E. (2025). Suppression of Ovarian Cancer Cell Proliferation Is Associated with Upregulation of Cell-Matrix Adhesion Programs and Integrin-\u03b24-Induced Cell Protection from Cisplatin. Cancers, 17.","DOI":"10.1101\/2025.02.10.637535"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e2150","DOI":"10.1002\/biof.2150","article-title":"Knockdown of integrin \u03b21 inhibits proliferation and promotes apoptosis in bladder cancer cells","volume":"51","author":"Wang","year":"2025","journal-title":"Biofactors"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e23688","DOI":"10.1002\/jbt.23688","article-title":"CD93 regulates breast cancer growth and vasculogenic mimicry through the PI3K\/AKT\/SP2 signaling pathway activated by integrin \u03b21","volume":"38","author":"Liu","year":"2024","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Guo, J., Santiago-O\u2019Farrill, J.M., Orellana, V., Ozyurt, R., Yang, H., Pina, M., Bildik, G., Mao, W., Bast, R.C., and Lu, Z. (2025). DIRAS3 Inhibits Ovarian Cancer Cell Growth by Blocking the Fibronectin-Mediated Integrin \u03b21\/FAK\/AKT Signaling Pathway. Cells, 14.","DOI":"10.3390\/cells14161250"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Siech, C., Rutz, J., Maxeiner, S., Grein, T., Sonnenburg, M., Tsaur, I., Chun, F.K., and Blaheta, R.A. (2022). Insulin-like Growth Factor-1 Influences Prostate Cancer Cell Growth and Invasion through an Integrin \u03b13, \u03b15, \u03b1V, and \u03b21 Dependent Mechanism. Cancers, 14.","DOI":"10.3390\/cancers14020363"},{"key":"ref_51","first-page":"2966","article-title":"Interfering with ITGB1-DT expression delays cancer progression and promotes cell sensitivity of NSCLC to cisplatin by inhibiting the MAPK\/ERK pathway","volume":"12","author":"Li","year":"2022","journal-title":"Am. J. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"118663","DOI":"10.1016\/j.bbamcr.2020.118663","article-title":"\u03b21-Integrin binding to collagen type 1 transmits breast cancer cells into chemoresistance by activating ABC efflux transporters","volume":"1867","author":"Baltes","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Cell. Res."},{"key":"ref_53","first-page":"531","article-title":"Integrin \u03b21 is a critical effector in promoting metastasis and chemo-resistance of esophageal squamous cell carcinoma","volume":"7","author":"Xu","year":"2017","journal-title":"Am. J. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"101496","DOI":"10.1016\/j.isci.2020.101496","article-title":"A Non-genetic Mechanism Involving the Integrin \u03b24\/Paxillin Axis Contributes to Chemoresistance in Lung Cancer","volume":"23","author":"Mohanty","year":"2020","journal-title":"iScience"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Xie, W., Hu, J., and Xu, H. (2025). Integrated transcriptomic analysis identifies lactylation-linked gemcitabine resistance and therapeutic targets in intrahepatic cholangiocarcinoma. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1611434"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"28633","DOI":"10.1038\/s41598-025-14067-z","article-title":"Integrin \u03b25 interacts with G3BP1 through activating FAK\/Src signaling pathway to promote gastric carcinogenesis","volume":"15","author":"Liu","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"9225","DOI":"10.1038\/s41598-025-93081-7","article-title":"ITGB5 is a prognostic factor in colorectal cancer and promotes cancer progression and metastasis through the Wnt signaling pathway","volume":"15","author":"Chen","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_58","first-page":"1108","article-title":"Cisplatin suppresses the growth and proliferation of breast and cervical cancer cell lines by inhibiting integrin \u03b25-mediated glycolysis","volume":"6","author":"Wang","year":"2016","journal-title":"Am. J. Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1007\/s12094-018-02025-3","article-title":"A comparative assessment of the effects of integrin inhibitor cilengitide on primary culture of head and neck squamous cell carcinoma (HNSCC) and HNSCC cell lines","volume":"21","author":"Zhang","year":"2019","journal-title":"Clin. Transl. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1042\/BST20240386","article-title":"The integrin adhesome and control of anti-tumour immunity","volume":"52","author":"Webb","year":"2024","journal-title":"Biochem. Soc. Trans."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1080\/13543784.2024.2417762","article-title":"Targeting a key FAK-tor: The therapeutic potential of combining focal adhesion kinase (FAK) inhibitors and chemotherapy for chemoresistant non-small cell lung cancer","volume":"33","author":"Geijerman","year":"2024","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"113116","DOI":"10.1016\/j.biopha.2022.113116","article-title":"Recent progress on FAK inhibitors with dual targeting capabilities for cancer treatment","volume":"151","author":"Wu","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1002\/pros.23476","article-title":"Effect of FAK inhibitor VS-6063 (defactinib) on docetaxel efficacy in prostate cancer","volume":"78","author":"Lin","year":"2018","journal-title":"Prostate"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5254","DOI":"10.1158\/1078-0432.CCR-22-0308","article-title":"Defactinib, Pembrolizumab, and Gemcitabine in Patients with Advanced Treatment Refractory Pancreatic Cancer: A Phase I Dose Escalation and Expansion Study","volume":"28","author":"Lim","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kryczka, J., Kryczka, J., Janczewski, \u0141., Gajda, A., Fr\u0105czyk, A., Boncela, J., Kolesi\u0144ska, B., and Brzezia\u0144ska-Lasota, E. (2022). Isothiocyanates (ITCs) 1-(Isothiocyanatomethyl)-4-phenylbenzene and 1-Isothiocyanato-3,5-bis(trifluoromethyl)benzene-Aldehyde Dehydrogenase (ALDH) Inhibitors, Decreases Cisplatin Tolerance and Migratory Ability of NSCLC. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158644"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Upadhyaya, B., Liu, Y., and Dey, M. (2019). Phenethyl Isothiocyanate Exposure Promotes Oxidative Stress and Suppresses Sp1 Transcription Factor in Cancer Stem Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051027"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s13402-019-00464-w","article-title":"Phenethyl isothiocyanate hampers growth and progression of HER2-positive breast and ovarian carcinoma by targeting their stem cell compartment","volume":"42","author":"Koschorke","year":"2019","journal-title":"Cell Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1007\/s12672-025-03824-1","article-title":"PEITC restores chemosensitivity in cisplatin-resistant non-small cell lung cancer by targeting c-Myc\/miR-424-5p","volume":"16","author":"Ding","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1002\/bit.28496","article-title":"Passage number of cancer cell lines: Importance, intricacies, and way-forward","volume":"120","author":"Prasad","year":"2023","journal-title":"Biotechnol. Bioeng."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Xie, H., Rutz, J., Maxeiner, S., Grein, T., Thomas, A., Juengel, E., Chun, F.K., Cinatl, J., Haferkamp, A., and Tsaur, I. (2022). Plant-Derived Sulforaphane Suppresses Growth and Proliferation of Drug-Sensitive and Drug-Resistant Bladder Cancer Cell Lines In Vitro. Cancers, 14.","DOI":"10.3390\/cancers14194682"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/3\/555\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T15:24:30Z","timestamp":1770305070000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/3\/555"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,5]]},"references-count":70,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["molecules31030555"],"URL":"https:\/\/doi.org\/10.3390\/molecules31030555","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,5]]}}}