{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T05:40:35Z","timestamp":1773294035399,"version":"3.50.1"},"reference-count":127,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Head and neck squamous cell carcinomas (HNSCC) are among the most common and lethal tumors worldwide, occurring mostly in oral cavity, pharynx, and larynx tissues. The squamous epithelia homeostasis is supported by the extracellular matrix (ECM), and alterations in this compartment are crucial for cancer development and progression. Laminin is a fundamental component of ECM, where it represents one of the main components of basement membrane (BM), and data supporting its contribution to HNSCC genesis and progression has been vastly explored in oral cavity squamous cell carcinoma. Laminin subtypes 111 (LN-111) and 332 (LN-332) are the main isoforms associated with malignant transformation, contributing to proliferation, adhesion, migration, invasion, and metastasis, due to its involvement in the regulation of several pathways associated with HNSCC carcinogenesis, including the activation of the EGFR\/MAPK signaling pathway. Therefore, it draws attention to the possibility that laminin may represent a convergence point in HNSCC natural history, and an attractive potential therapeutic target for these tumors.<\/jats:p>","DOI":"10.3390\/cancers13081890","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T01:37:25Z","timestamp":1618450645000},"page":"1890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Potential Therapeutic Significance of Laminin in Head and Neck Squamous Carcinomas"],"prefix":"10.3390","volume":"13","author":[{"given":"Nathalia","family":"Meireles Da Costa","sequence":"first","affiliation":[{"name":"Programa de Carcinog\u00eanese Molecular, Instituto Nacional de C\u00e2ncer\u2014INCA, Rua Andr\u00e9 Cavalcanti, 37-Centro, Rio de Janeiro 20231-050, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F\u00e1bio A.","family":"Mendes","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas, Pr\u00e9dio de Ci\u00eancias da Sa\u00fade\u2014Cidade Universit\u00e1ria, Universidade Federal do Rio de Janeiro, Ilha do Fund\u00e3o, A. Carlos Chagas, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0831-1204","authenticated-orcid":false,"given":"Bruno","family":"Pontes","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas, Pr\u00e9dio de Ci\u00eancias da Sa\u00fade\u2014Cidade Universit\u00e1ria, Universidade Federal do Rio de Janeiro, Ilha do Fund\u00e3o, A. Carlos Chagas, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2597-793X","authenticated-orcid":false,"given":"Luiz Eurico","family":"Nasciutti","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Intera\u00e7\u00f5es Celulares, Instituto de Ci\u00eancias Biom\u00e9dicas, Pr\u00e9dio de Ci\u00eancias da Sa\u00fade\u2014Cidade Universit\u00e1ria, Universidade Federal do Rio de Janeiro\u2014UFRJ, Ilha do Fund\u00e3o, A. Carlos Chagas, 373-bloco F, sala 26, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Felipe","family":"Ribeiro Pinto","sequence":"additional","affiliation":[{"name":"Programa de Carcinog\u00eanese Molecular, Instituto Nacional de C\u00e2ncer\u2014INCA, Rua Andr\u00e9 Cavalcanti, 37-Centro, Rio de Janeiro 20231-050, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Palumbo J\u00fanior","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Intera\u00e7\u00f5es Celulares, Instituto de Ci\u00eancias Biom\u00e9dicas, Pr\u00e9dio de Ci\u00eancias da Sa\u00fade\u2014Cidade Universit\u00e1ria, Universidade Federal do Rio de Janeiro\u2014UFRJ, Ilha do Fund\u00e3o, A. Carlos Chagas, 373-bloco F, sala 26, Rio de Janeiro 21941-902, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"310","article-title":"Head and Neck Cancers: New Etiological Insights","volume":"Volume 1","author":"Wild","year":"2020","journal-title":"World Cancer Report 2020"},{"key":"ref_3","unstructured":"National Cancer Institute (2020, September 12). Head and Neck Cancers, Available online: https:\/\/www.cancer.gov\/types\/head-and-neck\/head-neck-fact-sheet#what-are-cancers-of-the-head-and-neck."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"58","DOI":"10.4103\/0973-029X.131912","article-title":"Histological patterns of head and neck tumors: An insight to tumor histology","volume":"18","author":"Mishra","year":"2014","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/lio2.353","article-title":"Prognostic factors in laryngeal squamous cell carcinoma","volume":"5","author":"Bradford","year":"2020","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1159\/000381717","article-title":"Update on Head and Neck Cancer: Current Knowledge on Epidemiology, Risk Factors, Molecular Features and Novel Therapies","volume":"89","author":"Pezzuto","year":"2015","journal-title":"Oncology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.6004\/jnccn.2014.0142","article-title":"Head and neck cancers, version 2. 2014: Clinical practice guidelines in oncology","volume":"12","author":"Pfister","year":"2014","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1056\/NEJMra1715715","article-title":"Head and Neck Cancer","volume":"382","author":"Chow","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Network (2015). Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature, 517, 576\u2013582.","DOI":"10.1038\/nature14129"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.15252\/embr.201439246","article-title":"The extracellular matrix modulates the hallmarks of cancer","volume":"15","author":"Pickup","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Walker, C., Mojares, E., and Hern\u00e1ndez, A.D.R. (2018). Role of Extracellular Matrix in Development and Cancer Progression. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103028"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3390\/cells9020455","article-title":"Esophageal Cancer Development: Crucial Clues Arising from the Extracellular Matrix","volume":"9","author":"Palumbo","year":"2020","journal-title":"Cells"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3389\/fmolb.2019.00160","article-title":"Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy","volume":"6","author":"Henke","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2015.11.001","article-title":"Extracellular matrix structure","volume":"97","author":"Theocharis","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"R207","DOI":"10.1016\/j.cub.2017.02.006","article-title":"Basement membranes","volume":"27","author":"Jayadev","year":"2017","journal-title":"Curr. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1146\/annurev.bi.55.070186.005133","article-title":"Biochemical interactions of tumor cells with the basement membrane","volume":"55","author":"Liotta","year":"1986","journal-title":"Annu. Rev. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9933","DOI":"10.1016\/S0021-9258(19)83607-4","article-title":"Laminin--a glycoprotein from basement membranes","volume":"254","author":"Timpl","year":"1979","journal-title":"J. Biol. Chem."},{"key":"ref_18","first-page":"87","article-title":"Laminins and Cancer Progression","volume":"Volume 1","author":"Zent","year":"2009","journal-title":"Cell-Extracellular Matrix Interactions in Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.matbio.2016.08.007","article-title":"The opposing roles of laminin-binding integrins in cancer","volume":"57\u201358","author":"Ramovs","year":"2017","journal-title":"Matrix Biol."},{"key":"ref_20","first-page":"5570","article-title":"Laminin-5 gamma-2 (LAMC2) is highly expressed in anaplastic thyroid carcinoma and is associated with tumor progression, migration and invasion by modulating signaling of EGFR","volume":"74","author":"Garg","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nrc2089","article-title":"Tumour microenvironment: Laminin 332 in squamous-cell carcinoma","volume":"7","author":"Marinkovich","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0022-2836(81)90326-0","article-title":"Shapes, domain organizations and flexibility of laminin and fibronectin, two multifunctional proteins of the extracellular matrix","volume":"150","author":"Engel","year":"1981","journal-title":"J. Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"44504","DOI":"10.1074\/jbc.M402455200","article-title":"Molecular Analysis of Laminin N-terminal Domains Mediating Self-interactions","volume":"279","author":"Odenthal","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"48","DOI":"10.4161\/cam.22826","article-title":"The laminin family","volume":"7","author":"Aumailley","year":"2013","journal-title":"Cell Adhes. Migr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/j.1460-2075.1985.tb03630.x","article-title":"Evidence for coiled-coil alpha-helical regions in the long arm of laminin","volume":"4","author":"Paulsson","year":"1985","journal-title":"EMBO J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"30386","DOI":"10.1016\/S0021-9258(18)43825-2","article-title":"Assembly of synthetic laminin peptides into a triple-stranded coiled-coil structure","volume":"269","author":"Nomizu","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0945-053X(00)00072-X","article-title":"Structure and function of laminin LG modules","volume":"19","author":"Timpl","year":"2000","journal-title":"Matrix Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/bs.ctm.2015.07.002","article-title":"Molecular Basis of Laminin\u2013Integrin Interactions","volume":"76","author":"Yamada","year":"2015","journal-title":"Curr. Top. Membr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0945-053X(96)90157-2","article-title":"The functions of laminins: Lessons from in vivo studies","volume":"15","author":"Ryan","year":"1996","journal-title":"Matrix Biol."},{"key":"ref_30","first-page":"251","article-title":"Oral squamous cell carcinoma invasion is associated with a laminin-5 matrix re-organization but independent of basement membrane and hemidesmosome formation. clues from an in vitro invasion model","volume":"17","author":"Berndt","year":"1997","journal-title":"Invasion Metastasis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1002\/(SICI)1097-0142(19990601)85:11<2315::AID-CNCR3>3.0.CO;2-Y","article-title":"Clinocopathologic significance of laminin-5 \u03b32 chain expression in squamous cell carcinoma of the tongue: Immunohistochemical analysis of 67 lesions","volume":"85","author":"Ono","year":"1999","journal-title":"Cancer"},{"key":"ref_32","first-page":"509","article-title":"Laminin-5 as a predictor of invasiveness in cancer in situ lesions of the larynx","volume":"21","author":"Nordemar","year":"2001","journal-title":"Anticancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/1523-1747.ep12365531","article-title":"Expression and Topography of Integrins and Basement Membrane Proteins in Epidermal Carcinomas: Basal but not Squamous Cell Carcinomas Display Loss of \u03b16\u03b24 and BM-600\/Nicein","volume":"101","author":"Savoia","year":"1993","journal-title":"J. Investig. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/bcr1270","article-title":"Laminin isoform expression in breast tumors","volume":"7","author":"Holler","year":"2005","journal-title":"Breast Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/S0002-9440(10)64060-6","article-title":"Investigation into the mechanism of the loss of laminin 5 (\u03b13\u03b23\u03b32) expression in prostate cancer","volume":"158","author":"Hao","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/0092-8674(91)90092-D","article-title":"Epiligrin, a new cell adhesion ligand for integrin \u03b13\u03b21 in epithelial basement membranes","volume":"65","author":"Carter","year":"1991","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.tcb.2006.05.004","article-title":"Current insights into the formation and breakdown of hemidesmosomes","volume":"16","author":"Litjens","year":"2006","journal-title":"Trends Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1083\/jcb.200208145","article-title":"Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution","volume":"161","author":"Schenk","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4264","DOI":"10.1158\/0008-5472.CAN-06-4141","article-title":"A Laminin-Collagen Complex Drives Human Epidermal Carcinogenesis through Phosphoinositol-3-Kinase Activation","volume":"67","author":"Waterman","year":"2007","journal-title":"Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.matbio.2009.07.008","article-title":"Defining the role of laminin-332 in carcinoma","volume":"28","author":"Guess","year":"2009","journal-title":"Matrix Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1091\/mbc.e06-09-0806","article-title":"The short arm of laminin gamma2 chain of laminin-5 (laminin-332) binds syndecan-1 and regulates cellular adhesion and migration by suppressing phosphorylation of integrin beta4 chain","volume":"18","author":"Ogawa","year":"2007","journal-title":"Mol. Biol. Cell."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.soc.2015.03.006","article-title":"Cancer of the Oral Cavity","volume":"24","author":"Montero","year":"2015","journal-title":"Surg. Oncol. Clin. North Am."},{"key":"ref_43","first-page":"2119s","article-title":"Alcohol and cancer","volume":"52","author":"Blot","year":"1992","journal-title":"Cancer Res."},{"key":"ref_44","first-page":"3282","article-title":"Smoking and drinking in relation to oral and pharyngeal cancer","volume":"48","author":"Blot","year":"1988","journal-title":"Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1600-0714.1985.tb00488.x","article-title":"Distribution of fibronectin and laminin in oral leukoplakia and carcinoma","volume":"14","author":"Meyer","year":"1985","journal-title":"J. Oral Pathol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/hed.2880150208","article-title":"Clinical significance of laminin deposition and T-cell infiltration in oral cancer","volume":"15","author":"Noguchi","year":"1993","journal-title":"Head Neck"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/hed.2880160111","article-title":"Immunohistologic distribution of basement membrane in oral squamous cell carcinoma","volume":"16","author":"Kumagai","year":"1994","journal-title":"Head Neck"},{"key":"ref_48","first-page":"257","article-title":"An immunohistochemical study of the extracellular matrix in oral squamous cell carcinoma and its association with invasive and metastatic potential","volume":"424","author":"Harada","year":"1994","journal-title":"Virchows Arch. Pathol. Anat. Physiol. Klin. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1365-2559.1994.tb00571.x","article-title":"Alterations in expression of basement membrane proteins during tumour progression in oral mucosa","volume":"24","author":"Kannan","year":"2007","journal-title":"Histopathology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/j.1365-2133.1997.tb14938.x","article-title":"Altered distribution and synthesis of laminin-5 (kalinin) in oral lichen planus, epithelial dysplasias and squamous cell carcinomas","volume":"136","author":"Kainulainen","year":"1997","journal-title":"Br. J. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/sj.bjc.6690809","article-title":"Distribution of laminin and fibronectin isoforms in oral mucosa and oral squamous cell carcinoma","volume":"81","author":"Kosmehl","year":"1999","journal-title":"Br. J. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1007\/s004320000205","article-title":"Fibrillary co-deposition of laminin-5 and large unspliced tenascin-C in the invasive front of oral squamous cell carcinoma in vivo and in vitro","volume":"127","author":"Berndt","year":"2001","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1177\/002215540104901008","article-title":"A Comparative Quantitative Analysis of Laminin-5 in the Basement Membrane of Normal, Hyperplastic, and Malignant Oral Mucosa by Confocal Immunofluorescence Imaging","volume":"49","author":"Haas","year":"2001","journal-title":"J. Histochem. Cytochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/hed.20349","article-title":"Predictive value of laminin-5 and membrane type 1-matrix metalloproteinase expression for cervical lymph node metastasis in T1 and T2 squamous cell carcinomas of the tongue and floor of the mouth","volume":"28","author":"Kawano","year":"2006","journal-title":"Head Neck"},{"key":"ref_55","first-page":"3109","article-title":"The gamma2 chain of laminin-5 as an indicator of increased risk for recurrence in T1 stage tongue cancer","volume":"24","author":"Stoltzfus","year":"2004","journal-title":"Anticancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1002\/ijc.21568","article-title":"Expression of plasminogen activator inhibitor-1, urokinase receptor and laminin gamma-2 chain is an early coordinated event in incipient oral squamous cell carcinoma","volume":"118","author":"Lindberg","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.oraloncology.2005.06.013","article-title":"Diffuse expression of laminin gamma2 chain in disseminating and infiltrating cancer cells indicates a highly malignant state in advanced tongue cancer","volume":"42","author":"Kuratomi","year":"2006","journal-title":"Oral Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/jop.12121","article-title":"Laminin-5 gamma 2 chain expression is associated with intensity of tumor budding and density of stromal myofibroblasts in oral squamous cell carcinoma","volume":"43","author":"Junior","year":"2013","journal-title":"J. Oral Pathol. Med."},{"key":"ref_59","first-page":"793","article-title":"Prognostic value of differential expression of Laminin-5 gamma2 in oral squamous cell carcinomas: Correlation with survival","volume":"18","author":"Gasparoni","year":"2007","journal-title":"Oncol. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1158\/1078-0432.CCR-08-1816","article-title":"A Genetic Expression Profile Associated with Oral Cancer Identifies a Group of Patients at High Risk of Poor Survival","volume":"15","author":"Houck","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1111\/j.1365-2303.2006.00401.x","article-title":"Laminin-5 immunocytochemistry: A new tool for identifying dysplastic cells in oral brush biopsies","volume":"18","author":"Driemel","year":"2007","journal-title":"Cytopathology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1158\/1055-9965.EPI-07-2893","article-title":"Gene Expression Profiling Identifies Genes Predictive of Oral Squamous Cell Carcinoma","volume":"17","author":"Chen","year":"2008","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.yexcr.2005.05.013","article-title":"Suppression of laminin-5 expression leads to increased motility, tumorigenicity, and invasion","volume":"309","author":"Yuen","year":"2005","journal-title":"Exp. Cell Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5251","DOI":"10.1158\/0008-5472.CAN-05-4478","article-title":"Tight junction protein claudin-1 enhances the invasive activity of oral squamous cell carcinoma cells by promoting cleavage of laminin-5 gamma2 chain via matrix metalloproteinase (MMP)-2 and membrane-type MMP-1","volume":"66","author":"Oku","year":"2006","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Yasuda, H., Nakagawa, M., Kiyokawa, H., Yoshida, E., Yoshimura, T., Koshikawa, N., Itoh, F., and Seiki, M. (2019). Unique Biological Activity and Potential Role of Monomeric Laminin-\u03b32 as a Novel Biomarker for Hepatocellular Carcinoma: A Review. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010226"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1083\/jcb.145.6.1309","article-title":"Targeted Disruption of the LAMA3 Gene in Mice Reveals Abnormalities in Survival and Late Stage Differentiation of Epithelial Cells","volume":"145","author":"Ryan","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1242\/jcs.112.17.2925","article-title":"(Alpha)3(beta)1 integrin regulates epithelial cytoskeletal organization","volume":"112","author":"Wang","year":"1999","journal-title":"J. Cell Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/j.1600-0714.2010.00936.x","article-title":"EGF\/TGF\u03b21 co-stimulation of oral squamous cell carcinoma cells causes an epithelial-mesenchymal transition cell phenotype expressing laminin 332","volume":"40","author":"Richter","year":"2010","journal-title":"J. Oral Pathol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1242\/jcs.00389","article-title":"Regulation of tight junctions during the epithelium-mesenchyme transition: Direct repression of the gene expression of claudins\/occludin by Snail","volume":"116","author":"Ikenouchi","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1016\/j.ajpath.2012.02.028","article-title":"MAPK\/ERK-Dependent Translation Factor Hyperactivation and Dysregulated Laminin \u03b32 Expression in Oral Dysplasia and Squamous Cell Carcinoma","volume":"180","author":"Degen","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0304-3835(01)00682-6","article-title":"Epidermal growth factor receptor gene amplification is correlated with laminin-5 gamma2 chain expression in oral squamous cell carcinoma cell lines","volume":"175","author":"Ono","year":"2002","journal-title":"Cancer Lett."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrc1840","article-title":"Oncomirs\u2014MicroRNAs with a role in cancer","volume":"6","author":"Slack","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1038\/bjc.2013.607","article-title":"Tumour-suppressive microRNA-29s inhibit cancer cell migration and invasion by targeting laminin\u2013integrin signalling in head and neck squamous cell carcinoma","volume":"109","author":"Kinoshita","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3233\/CBM-191362","article-title":"MicroRNA-134 inhibits tumor stem cell migration and invasion in oral squamous cell carcinomas via downregulation of PI3K-Akt signaling pathway by inhibiting LAMC2 expression","volume":"29","author":"Zhou","year":"2020","journal-title":"Cancer Biomark."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1111\/jop.12677","article-title":"LINC00511 interacts with miR-765 and modulates tongue squamous cell carcinoma progression by targeting LAMC2","volume":"47","author":"Ding","year":"2018","journal-title":"J. Oral Pathol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1002\/ijc.32027","article-title":"Laminin \u03b32-enriched extracellular vesicles of oral squamous cell carcinoma cells enhance in vitro lymphangiogenesis via integrin \u03b13-dependent uptake by lymphatic endothelial cells","volume":"144","author":"Wang","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4232","DOI":"10.1038\/sj.onc.1208601","article-title":"Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma","volume":"24","author":"Snijders","year":"2005","journal-title":"Oncogene"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.archoralbio.2014.07.005","article-title":"The role of components of the extracellular matrix and inflammation on oral squamous cell carcinoma metastasis","volume":"59","author":"Tanis","year":"2014","journal-title":"Arch. Oral Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s13277-009-0008-x","article-title":"Laminin-derived peptide AG73 regulates migration, invasion, and protease activity of human oral squamous cell carcinoma cells through syndecan-1 and beta1 integrin","volume":"31","author":"Siqueira","year":"2010","journal-title":"Tumour Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"47904","DOI":"10.18632\/oncotarget.10062","article-title":"Laminin-111 peptide C16 regulates invadopodia activity of malignant cells through \u03b21 integrin, Src and ERK \u00bd","volume":"7","author":"Siqueira","year":"2016","journal-title":"Oncotarget"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.oraloncology.2018.09.025","article-title":"Hypopharyngeal cancer: A state of the art review","volume":"86","author":"Garneau","year":"2018","journal-title":"Oral Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0140-6736(19)30956-0","article-title":"Nasopharyngeal carcinoma","volume":"394","author":"Chen","year":"2019","journal-title":"Lancet"},{"key":"ref_84","first-page":"1","article-title":"Nasopharyngeal Cancer","volume":"Volume 1","author":"Sinha","year":"2020","journal-title":"StatPearls"},{"key":"ref_85","first-page":"443","article-title":"Epstein\u2013Barr virus-associated antibody patterns in carcinoma of the post-nasal space","volume":"5","author":"Friberg","year":"1969","journal-title":"Clin. Exp. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s10555-017-9693-x","article-title":"Progression of understanding for the role of Epstein-Barr virus and management of nasopharyngeal carcinoma","volume":"36","author":"Nakanishi","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1001\/jama.1971.03180360064009","article-title":"Antibody to Epstein-Barr virus in American patients with carcinoma of the nasopharynx","volume":"216","author":"Goldman","year":"1971","journal-title":"JAMA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0167-4781(01)00260-3","article-title":"Identification of downstream target genes of latent membrane protein 1 in nasopharyngeal carcinoma cells by suppression subtractive hybridization","volume":"1520","author":"Lo","year":"2001","journal-title":"Biochim. Biophys. Acta Gene Struct. Expr."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1177\/000348949910800906","article-title":"Expression of Epstein-Barr Virus Latent Membrane Proteins Leads to Changes in Keratinocyte Cell Adhesion","volume":"108","author":"Farwell","year":"1999","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5874","DOI":"10.1073\/pnas.0801130105","article-title":"MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins","volume":"105","author":"Sengupta","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1080\/00016480252814298","article-title":"Differential Expression and Topography of Adhesion Molecules in Laryngeal and Oropharyngeal Carcinomas","volume":"122","author":"Ricci","year":"2002","journal-title":"Acta Oto-Laryngol."},{"key":"ref_92","first-page":"5193","article-title":"Biosynthesis and secretion of laminin and laminin-associated glycoproteins by nonmalignant and malignant human keratinocytes: Comparison of cell lines from primary and secondary tumors in the same patient","volume":"48","author":"Frenette","year":"1988","journal-title":"Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1097\/00005537-200407000-00022","article-title":"Increased Expression of Laminin-5 and Its Prognostic Significance in Hypopharyngeal Cancer","volume":"114","author":"Nakayama","year":"2004","journal-title":"Laryngoscope"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1177\/0194599811430818","article-title":"The necessity of dissection of level IIb in laryngeal squamous cell carcinoma: A clinical study","volume":"146","author":"Aslan","year":"2012","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/em.21920","article-title":"Gene-environment interactions in determining differences in genetic susceptibility to cancer in subsites of the head and neck","volume":"56","author":"Maurya","year":"2014","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_96","first-page":"5519","article-title":"LAMP3 and TP53 overexpression predicts poor outcome in laryngeal squamous cell carcinoma","volume":"8","author":"Qiu","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s10585-013-9630-5","article-title":"Immunohistochemical markers of distant metastasis in laryngeal and hypopharyngeal squamous cell carcinomas","volume":"31","author":"Rodrigo","year":"2014","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-019-0983-5","article-title":"Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: A systematic review","volume":"18","author":"Peltanova","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_99","first-page":"1193","article-title":"Morphological aspects of basement-membranes and their receptors in benign and malignant neoplasms (review)","volume":"6","author":"Nerlich","year":"1995","journal-title":"Int. J. Oncol."},{"key":"ref_100","first-page":"201","article-title":"Prognostic aspects of the loss of epithelial basement membrane components in preinvasive and invasive laryngeal carcinomas","volume":"18","author":"Hagedorn","year":"1998","journal-title":"Anticancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0046-8177(98)90059-4","article-title":"Defective basement membrane in laryngeal carcinomas with heterogeneous loss of distinct components","volume":"29","author":"Hagedorn","year":"1998","journal-title":"Hum. Pathol."},{"key":"ref_102","first-page":"1045","article-title":"Divergence in distribution and prognostic significance of major basement components in laryngeal carcinomas","volume":"18","author":"Hagedorn","year":"2001","journal-title":"Int. J. Oncol."},{"key":"ref_103","first-page":"4985","article-title":"Laminin-5 gamma 2: A marker to identify oral mucosal lesions at risk for tumor development?","volume":"23","author":"Nordemar","year":"2003","journal-title":"Anticancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1111\/1523-1747.ep12324108","article-title":"gamma 2 chain of laminin-5 is recognized by monoclonal antibody GB3","volume":"105","author":"Matsui","year":"1995","journal-title":"J. Investig. Dermatol."},{"key":"ref_105","first-page":"5691","article-title":"Role of laminin receptor in tumor cell migration","volume":"47","author":"Wewer","year":"1987","journal-title":"Cancer Res."},{"key":"ref_106","first-page":"4132","article-title":"Laminin-5 is a marker of invading cancer cells in some human carcinomas and is coexpressed with the receptor for urokinase plasminogen activator in budding cancer cells in colon adenocarcinomas","volume":"55","author":"Pyke","year":"1995","journal-title":"Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S1044-579X(02)00025-1","article-title":"Putative role of 67 kDa elastin-laminin receptor in tumor invasion","volume":"12","author":"Larbi","year":"2002","journal-title":"Semin. Cancer Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/01.mlg.0000184505.05662.b9","article-title":"67-kDa Laminin Receptor in Human Laryngeal Squamous Cell Carcinoma","volume":"116","author":"Zhou","year":"2006","journal-title":"Laryngoscope"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/0006-291X(90)91144-H","article-title":"Laminin and fibronectin increase the steady state level of the 67 kD high affinity metastasis-associated laminin receptor mRNA in human cancer cells","volume":"168","author":"Castronovo","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1016\/S0021-9258(17)36025-8","article-title":"Laminin increases the release of type IV collagenase from malignant cells","volume":"261","author":"Thorgeirsson","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1677\/erc.1.00870","article-title":"The 67 kDa laminin receptor increases tumor aggressiveness by remodeling laminin-1","volume":"12","author":"Berno","year":"2005","journal-title":"Endocr. Relat. Cancer."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1007\/s00405-008-0666-0","article-title":"Laminin expression in advanced laryngeal squamous cell carcinoma does not correlate to neck metastases","volume":"265","author":"Olofsson","year":"2008","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1158\/0008-5472.CAN-07-6160","article-title":"Targeting a Tumor-Specific Laminin Domain Critical for Human Carcinogenesis","volume":"68","author":"Tran","year":"2008","journal-title":"Cancer Res."},{"key":"ref_114","first-page":"1173","article-title":"Targeting the tumor microenvironment with chemically modified tetracyclines: Inhibition of laminin 5 gamma2 chain promigratory fragments and vasculogenic mimicry","volume":"1","author":"Seftor","year":"2002","journal-title":"Mol. Cancer Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1093\/carcin\/bgl005","article-title":"Synthetic D-amino acid peptide inhibits tumor cell motility on laminin-5","volume":"27","author":"Sroka","year":"2006","journal-title":"Carcinogenesis"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1111\/j.1349-7006.2006.00291.x","article-title":"Identification of oligopeptides binding to peritoneal tumors of gastric cancer","volume":"97","author":"Akita","year":"2006","journal-title":"Cancer Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1042\/BSR20070004","article-title":"The 67 kDa laminin receptor: Structure, function and role in disease","volume":"28","author":"Nelson","year":"2008","journal-title":"Biosci. Rep."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The Hallmarks of Cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1080\/13543776.2019.1693543","article-title":"Patented therapeutic approaches targeting LRP\/LR for cancer treatment","volume":"29","author":"Vania","year":"2019","journal-title":"Expert Opin. Ther. Patents"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"10884","DOI":"10.1073\/pnas.1519676113","article-title":"Distinct biological events generated by ECM proteolysis by two homologous collagenases","volume":"113","author":"Solomonov","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1016\/j.bbamcr.2017.06.009","article-title":"Next generation matrix metalloproteinase inhibitors\u2014Novel strategies bring new prospects","volume":"1864","author":"Levin","year":"2017","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s40425-018-0376-0","article-title":"Tumor matrix remodeling and novel immunotherapies: The promise of matrix-derived immune biomarkers","volume":"6","author":"Mushtaq","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_123","first-page":"58","article-title":"Laminin \u03b32-mediating T cell exclusion attenuates response to anti-PD-1 therapy","volume":"7","author":"Li","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/00001665-200503000-00005","article-title":"Effect of Induction Chemotherapy on Changes of Laminin and Syndecan Expression in Oral Squamous Cell Carcinomas: A Prospective, Randomized, Clinicopathologic and Immunohistochemical Study","volume":"16","author":"Szigeti","year":"2005","journal-title":"J. Craniofacial Surg."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.4161\/cbt.6.11.4858","article-title":"Chemoradiation-induced expression of fibroblast growth factor-2 and laminin in patients with cervical cancer","volume":"6","author":"Nakawatari","year":"2007","journal-title":"Cancer Biol. Ther."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.2147\/OTT.S93720","article-title":"Molecularly targeted therapy for the treatment of head and neck cancer: A review of the ErbB family inhibitors","volume":"9","author":"Worden","year":"2016","journal-title":"OncoTargets Ther."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.3802\/jgo.2020.31.e11","article-title":"LAMC1 is a prognostic factor and a potential therapeutic target in endometrial cancer","volume":"31","author":"Kunitomi","year":"2020","journal-title":"J. Gynecol. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/8\/1890\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:48:09Z","timestamp":1760161689000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/8\/1890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,15]]},"references-count":127,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["cancers13081890"],"URL":"https:\/\/doi.org\/10.3390\/cancers13081890","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,15]]}}}