title: Slug is associated with poor survival in squamous cell carcinoma of the lung.
abstract: We investigated the expression of slug in a large set of lung squamous and adenocarcinomas to determine common or dissimilar features in its expression in these two most common forms of lung cancer. To investigate slug related tumor spread we studied the expression of vimentin, claudin 1, MMP2 and MMP9 in these tumors and their relation to slug. Addition, cell invasion assays, mRNA analysis and zymographic tests were performed to study epitheliomesenchymal transition (EMT) related changes in slug blocked lung cell lines. According to the results slug expression did not significantly differ between squamous (SCC) and adenocarcinoma (AC) (P = 0.25). In SCC, slug associated with vimentin (P = 0.016). In AC, claudin 1 associated with MMP2 (P = 0.037). In SCC slug expression had a poor prognositic significance (P = 0.006) and it had independent prognostic value (P = 0.037). In AC MMP2 had a worsening impact on survival (P = 0.021) and it had independent prognostic value (P = 0.002). In cell invasion assays, slug knockdown inhibited the invasion and migration of BEAS-2B, SK-LU1 and SK-MES1 cell lines. The mRNA expression of claudin 1 was downregulated in SK-LU1 cell line. Both tumor cell lines expressed MMP2 and in SK-MES1 slug inhibited line MMP2 appeared to decrease. The results show that slug associated EMT is more pronounced in lung SCC than AC. Slug associated with vimentin in SCC and had an independent prognostic value in this tumor type. Forced slug inhibition might be one putative way of treatment of SCC of the lung.
authors.affiliation: Department of Internal Medicine, Pulmonary Division, University of Oulu and Oulu University Hospital Finland ; Medical Research Center Oulu, Oulu University Hospital and University of Oulu Finland.
authors.forename: Heta
authors.initials: H
authors.lastname: Merikallio
authors.affiliation: Department of Oncology and Hematology, University Hospital of Oulu, University of Oulu Finland.
authors.forename: Taina Turpeenniemi-Hujanen
authors.initials: TT
authors.lastname: T
authors.affiliation: Department of Pathology, University Hospital of Oulu Oulu, Finland.
authors.forename: Paavo
authors.initials: P
authors.lastname: Pääkkö
authors.affiliation: Department of Internal Medicine, Pulmonary Division, University of Oulu and Oulu University Hospital Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Mäkitaro
authors.affiliation: Department of Internal Medicine, Pulmonary Division, University of Oulu and Oulu University Hospital Finland ; Medical Research Center Oulu, Oulu University Hospital and University of Oulu Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Kaarteenaho
authors.affiliation: Medical Research Center Oulu, Oulu University Hospital and University of Oulu Finland ; Institute of Biomedicine, Department of Anatomy and Cell Biology, University of Oulu and Department of Surgery, Oulu University Hospital Finland.
authors.forename: Siri
authors.initials: S
authors.lastname: Lehtonen
authors.affiliation: Department of Dentistry, University of Oulu Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Salo
authors.affiliation: Department of Dentistry, University of Oulu Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
authors.affiliation: Department of Internal Medicine, Pulmonary Division, University of Oulu and Oulu University Hospital Finland ; Medical Research Center Oulu, Oulu University Hospital and University of Oulu Finland.
authors.forename: Terttu
authors.initials: T
authors.lastname: Harju
authors.affiliation: Department of Pathology and Forensic Medicine, University of Eastern Finland, Kuopio and Cancer Center of Eastern Finland Kuopio, Finland.
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D062445:Claudin-1 / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014746:Vimentin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C568108:CLDN1 protein, human; D062445:Claudin-1; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: EMT; MMP; Slug; carcinoma; claudin 1; lung; vimentin