{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:28:42Z","timestamp":1790782122697,"version":"4.1.0"},"reference-count":68,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,31]],"date-time":"2021-10-31T00:00:00Z","timestamp":1635638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fibulins (FBLNs), interacting with cell adhesion receptors and extracellular matrix (ECM) components, play multiple roles in ECM structures and tissue functions. Abnormal expression of FBLN2, one of the fibulin family members, contributes to tumor initiation and development. However, the function of FBLN2 in human non-small cell lung cancer (NSCLC) has not yet been elucidated. In this study, we found that FBLN2 was downregulated in 9 out of 11 lung cancer cell lines compared to normal bronchial epithelial cells, which was associated with DNA hypermethylation. Primary lung squamous cell carcinoma expressed significantly more FBLN2 protein compared to adenocarcinoma (p = 0.047). Ectopic expression of FBLN2 led to decreased cell proliferation, migration and invasion, accompanied by inactivated MAPK\/ERK and AKT\/mTOR pathways, while FBLN2 siRNA knockdown resulted in an opposite biological behaviour in NSCLC cells. Additionally, overexpression of FBLN2 led to dysregulation of cell adhesion molecules, ECM markers and a panel of lysate\/exosome-derived-microRNAs, which are involved in cell adhesion and ECM remodelling. Taken together, our data indicate that FBLN2 is methylated and exerts a tumor suppressor function through modulation of MAPK\/ERK and AKT pathways and regulation of cell adhesion and ECM genes. Moreover, FBLN2 might be a potential biomarker for the sub-classification of NSCLC.<\/jats:p>","DOI":"10.3390\/ijms222111834","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:21:34Z","timestamp":1635805294000},"page":"11834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7409-4001","authenticated-orcid":false,"given":"Yunxia","family":"Ma","sequence":"first","affiliation":[{"name":"Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7976-2611","authenticated-orcid":false,"given":"Miljana","family":"Nenkov","sequence":"additional","affiliation":[{"name":"Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8274-8271","authenticated-orcid":false,"given":"Desiree Charlotte","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Abubrig","sequence":"additional","affiliation":[{"name":"Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Gassler","sequence":"additional","affiliation":[{"name":"Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4752-9222","authenticated-orcid":false,"given":"Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.canlet.2012.06.019","article-title":"The dual role of fibulins in tumorigenesis","volume":"325","author":"Obaya","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.matbio.2014.02.004","article-title":"Fibulin-4 and fibulin-5 in elastogenesis and beyond: Insights from mouse and human studies","volume":"37","author":"Papke","year":"2014","journal-title":"Matrix Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1242\/jcs.115.14.2817","article-title":"Elastic fibres","volume":"115","author":"Kielty","year":"2002","journal-title":"J. Cell Sci."},{"key":"ref_4","unstructured":"(2021, September 29). Atlas, Human Protein. Available online: https:\/\/www.proteinatlas.org\/ENSG00000163520-FBLN2\/tissue."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1128\/MCB.01876-07","article-title":"Fibulin-2 is dispensable for mouse development and elastic fiber formation","volume":"28","author":"Sicot","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1161\/ATVBAHA.109.196725","article-title":"Fibulin-2 and fibulin-5 cooperatively function to form the internal elastic lamina and protect from vascular injury","volume":"30","author":"Chapman","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3811","DOI":"10.1007\/s00018-014-1577-4","article-title":"Fibulin-2 is involved in early extracellular matrix development of the outgrowing mouse mammary epithelium","volume":"71","author":"Olijnyk","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"14139","DOI":"10.1038\/s41598-018-32507-x","article-title":"Fibulin-2 is required for basement membrane integrity of mammary epithelium","volume":"8","author":"Ibrahim","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1038\/jid.2014.166","article-title":"Regulation of fibulin-2 gene expression by integrin \u03b13\u03b21 contributes to the invasive phenotype of transformed keratinocytes","volume":"134","author":"Missan","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1038\/jid.2014.10","article-title":"Reduced fibulin-2 contributes to loss of basement membrane integrity and skin blistering in mice lacking integrin \u03b13\u03b21 in the epidermis","volume":"134","author":"Longmate","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/bph.14195","article-title":"The extracellular matrix as a key regulator of intracellular signalling networks","volume":"176","author":"Hastings","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.molmed.2005.06.001","article-title":"Fibulins and cancer: Friend or foe?","volume":"11","author":"Gallagher","year":"2005","journal-title":"Trends Mol. Med."},{"key":"ref_13","unstructured":"(2021, September 29). Atlas, Genetics and Cytogenetics in Oncology and Haematology. Available online: http:\/\/atlasgeneticsoncology.org\/Genes\/GC_FBLN2.html."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1046\/j.1432-1327.1999.00523.x","article-title":"Mouse fibulin-2 gene. Complete exon-intron organization and promoter characterization","volume":"263","author":"Sicot","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/onc.2011.272","article-title":"Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma","volume":"31","author":"Law","year":"2012","journal-title":"Oncogene"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5130","DOI":"10.1093\/nar\/gkv210","article-title":"Identification of recurrent regulated alternative splicing events across human solid tumors","volume":"43","author":"Eisenberg","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yang, I.S., Son, H., Kim, S., and Kim, S. (2016). ISOexpresso: A web-based platform for isoform-level expression analysis in human cancer. BMC Genom., 17.","DOI":"10.1186\/s12864-016-2852-6"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3346","DOI":"10.1038\/onc.2011.505","article-title":"Role of MUC4-NIDO domain in the MUC4-mediated metastasis of pancreatic cancer cells","volume":"31","author":"Senapati","year":"2012","journal-title":"Oncogene"},{"key":"ref_19","first-page":"2799","article-title":"Fibulin-2 inhibits development of gastric cancer by downregulating \u03b2-catenin","volume":"18","author":"Ma","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_20","unstructured":"(2021, September 29). Atlas, Human Protein. Available online: https:\/\/www.proteinatlas.org\/ENSG00000163520-FBLN2."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sofela, A.A., Hilton, D.A., Ammoun, S., Baiz, D., Adams, C.L., Ercolano, E., Jenkinson, M.D., Kurian, K.M., Teo, M., and Whitfield, P.C. (2021). Fibulin-2: A Novel Biomarker for Differentiating Grade II from Grade I Meningiomas. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020560"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Baird, B.N., Schliekelman, M.J., Ahn, Y.H., Chen, Y., Roybal, J.D., Gill, B.J., Mishra, D.K., Erez, B., O\u2019Reilly, M., and Yang, Y. (2013). Fibulin-2 is a driver of malignant progression in lung adenocarcinoma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067054"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1242\/jcs.081513","article-title":"Roles for microRNAs in the regulation of cell adhesion molecules","volume":"124","author":"Valastyan","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/iep.12079","article-title":"Illustrating the interplay between the extracellular matrix and microRNAs","volume":"95","author":"Piccinini","year":"2014","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1161\/CIRCRESAHA.111.255737","article-title":"MicroRNA-29 in aortic dilation: Implications for aneurysm formation","volume":"109","author":"Boon","year":"2011","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/1476-4598-9-51","article-title":"Identification of 5 novel genes methylated in breast and other epithelial cancers","volume":"9","author":"Hill","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.cell.2008.06.020","article-title":"SnapShot: Ras Signaling","volume":"133","author":"Cully","year":"2008","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/5584_2016_219","article-title":"The Role of Dysregulated MicroRNA Expression in Lung Cancer","volume":"911","author":"Krutakova","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_29","first-page":"13","article-title":"The emerging role of extracellular vesicle-derived miRNAs: Implication in cancer progression and stem cell related diseases","volume":"2","author":"Yang","year":"2016","journal-title":"J. Clin. Epigenet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/path.4469","article-title":"HOPX is methylated and exerts tumour-suppressive function through Ras-induced senescence in human lung cancer","volume":"235","author":"Chen","year":"2015","journal-title":"J. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1002\/ijc.22753","article-title":"Homeobox gene HOP has a potential tumor suppressive activity in human lung cancer","volume":"121","author":"Chen","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ma, Y., Schr\u00f6der, D.C., Nenkov, M., Rizwan, M.N., Abubrig, M., Sonnemann, J., Murrieta-Coxca, J.M., Morales-Prieto, D.M., Westermann, M., and Ga\u00dfler, N. (2021). Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062944"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.2353\/ajpath.2007.060478","article-title":"Loss of fibulin-2 expression is associated with breast cancer progression","volume":"170","author":"Yi","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_34","unstructured":"Decapmaker, Z. (2018). The Role of Fibulin-2 in ECM-Driven Resistance to Targeted Therapy of Head and Neck Squamous Cell Carcinoma. [Master\u2019s Thesis, Ghent University]."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/978-3-319-43624-1_7","article-title":"The Role of DNA Methylation in Cancer","volume":"945","author":"Lakshminarasimhan","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/5947","article-title":"Cancer epigenetics comes of age","volume":"21","author":"Jones","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"185","DOI":"10.4161\/epi.4.3.8752","article-title":"Epigenetic analysis of childhood acute lymphoblastic leukemia","volume":"4","author":"Dunwell","year":"2009","journal-title":"Epigenetics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.3892\/ol.2017.6506","article-title":"Identification of novel methylated targets in colorectal cancer by microarray analysis and construction of co-expression network","volume":"14","author":"Li","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhong, W., Myers, J.S., Wang, F., Wang, K., Lucas, J., Rosfjord, E., Lucas, J., Hooper, A.T., Yang, S., and Lemon, L.A. (2020). Comparison of the molecular and cellular phenotypes of common mouse syngeneic models with human tumors. BMC Genom., 21.","DOI":"10.1186\/s12864-019-6344-3"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"501","DOI":"10.2967\/jnumed.109.065706","article-title":"Of mice and humans: Are they the same?\u2014Implications in cancer translational research","volume":"51","author":"Maina","year":"2010","journal-title":"J. Nucl. Med."},{"key":"ref_41","first-page":"e918099","article-title":"Roles of Fibulin-2 in Carcinogenesis","volume":"26","author":"Zhang","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_42","first-page":"1997","article-title":"ERK\/MAPK signalling pathway and tumorigenesis","volume":"19","author":"Guo","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3389\/fonc.2014.00064","article-title":"Targeting PI3K\/Akt\/mTOR Signaling in Cancer","volume":"4","author":"Porta","year":"2014","journal-title":"Front. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3892\/or.2013.2799","article-title":"Role of fibulin-3 in lung cancer: In vivo and in vitro analyses","volume":"31","author":"Xu","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10594","DOI":"10.1038\/s41598-018-28906-9","article-title":"Fibulin-3 knockdown inhibits cervical cancer cell growth and metastasis in vitro and in vivo","volume":"8","author":"Li","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.3892\/ol.2017.6539","article-title":"Loss of fibulin-2 expression is involved in the inhibition of breast cancer invasion and forms a new barrier in addition to the basement membrane","volume":"14","author":"Tan","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.3892\/ijo.2017.3921","article-title":"Fibulin-4 promotes osteosarcoma invasion and metastasis by inducing epithelial to mesenchymal transition via the PI3K\/Akt\/mTOR pathway","volume":"50","author":"Zhang","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_48","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-integrin signalling in head and neck squamous cell carcinoma","volume":"109","author":"Kinoshita","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3663","DOI":"10.18632\/oncotarget.23194","article-title":"Inhibition of integrin \u03b21-mediated oncogenic signalling by the antitumor microRNA-29 family in head and neck squamous cell carcinoma","volume":"9","author":"Koshizuka","year":"2018","journal-title":"Oncotarget"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"13027","DOI":"10.1073\/pnas.0805038105","article-title":"Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis","volume":"105","author":"Sutherland","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7670","DOI":"10.1158\/0008-5472.CAN-11-0964","article-title":"Targets of the tumor suppressor miR-200 in regulation of the epithelial-mesenchymal transition in cancer","volume":"71","author":"Schliekelman","year":"2011","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1042\/CS20200573","article-title":"Sepsis plasma-derived exosomal miR-1-3p induces endothelial cell dysfunction by targeting SERP1","volume":"135","author":"Gao","year":"2021","journal-title":"Clin. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Liu, Q., Peng, F., and Chen, J. (2019). The Role of Exosomal MicroRNAs in the Tumor Microenvironment of Breast Cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20163884"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Santos, P., and Almeida, F. (2020). Role of Exosomal miRNAs and the Tumor Microenvironment in Drug Resistance. Cells, 9.","DOI":"10.3390\/cells9061450"},{"key":"ref_55","first-page":"1500","article-title":"Non-Exosomal and Exosomal Circulatory MicroRNAs: Which Are More Valid as Biomarkers?","volume":"10","author":"Shahidan","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1533033819892590","DOI":"10.1177\/1533033819892590","article-title":"MiR-200b-3p Functions as an Oncogene by Targeting ABCA1 in Lung Adenocarcinoma","volume":"18","author":"Liu","year":"2019","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/j.biopha.2017.11.105","article-title":"MiR-9-5p promotes cell growth and metastasis in non-small cell lung cancer through the repression of TGFBR2","volume":"96","author":"Li","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"BSR20171265","DOI":"10.1042\/BSR20171265","article-title":"MiR-29a: A potential therapeutic target and promising biomarker in tumors","volume":"38","author":"Wang","year":"2018","journal-title":"Biosci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3389\/fonc.2019.00120","article-title":"MiR-1-3p Inhibits Lung Adenocarcinoma Cell Tumorigenesis via Targeting Protein Regulator of Cytokinesis 1","volume":"9","author":"Li","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.7150\/jca.29426","article-title":"MiR-199a-5p suppresses non-small cell lung cancer via targeting MAP3K11","volume":"10","author":"Li","year":"2019","journal-title":"J. Cancer"},{"key":"ref_61","first-page":"2252","article-title":"MicroRNA-19a-3p inhibits the cellular proliferation and invasion of non-small cell lung cancer by downregulating UBAP2L","volume":"20","author":"Pan","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_62","first-page":"2444","article-title":"MicroRNA-155-5p suppresses the migration and invasion of lung adenocarcinoma A549 cells by targeting Smad2","volume":"16","author":"Lin","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1010428317697579","DOI":"10.1177\/1010428317697579","article-title":"MicroRNA-125a-5p plays a role as a tumor suppressor in lung carcinoma cells by directly targeting STAT3","volume":"39","author":"Zhong","year":"2017","journal-title":"Tumour Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"978","DOI":"10.2174\/092986708784049667","article-title":"ANTI-ADHESION evolves to a promising therapeutic concept in oncology","volume":"15","author":"Schmidmaier","year":"2008","journal-title":"Curr. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1158\/1078-0432.CCR-17-1628","article-title":"Development of a Function-Blocking Antibody Against Fibulin-3 as a Targeted Reagent for Glioblastoma","volume":"24","author":"Nandhu","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"14084","DOI":"10.18632\/oncotarget.23505","article-title":"Cystatin A suppresses tumor cell growth through inhibiting epithelial to mesenchymal transition in human lung cancer","volume":"9","author":"Ma","year":"2018","journal-title":"Oncotarget"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/ijc.20498","article-title":"Downregulation of connexin 26 in human lung cancer is related to promoter methylation","volume":"113","author":"Chen","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1038\/nprot.2006.339","article-title":"Clonogenic assay of cells in vitro","volume":"1","author":"Franken","year":"2006","journal-title":"Nat. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11834\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:23:55Z","timestamp":1760167435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,31]]},"references-count":68,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222111834"],"URL":"https:\/\/doi.org\/10.3390\/ijms222111834","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,31]]}}}