title: Sec62 bridges the gap from 3q amplification to molecular cell biology in non-small cell lung cancer.
abstract: The molecular carcinogenesis of lung cancer has yet to be clearly elucidated. We investigated the possible oncogenic function of SEC62 in lung cancer, which was predicted based on our previous findings that lung and thyroid cancer tissue samples exhibited increased Sec62 protein levels. The SEC62 gene locus is at 3q26.2, and 3q amplification is reportedly the most common genomic alteration in non-small cell lung cancer. We analyzed SEC62 mRNA and protein levels in tissue samples from lung cancer patients by real-time quantitative PCR, Western blot, and IHC and found significantly increased SEC62 mRNA and protein levels in tumors compared with tumor-free tissue samples from the same patients. Correlation analyses revealed significantly higher Sec62 levels in tumors with lymph node metastases compared with nonmetastatic tumors, as well as in poorly compared with moderately differentiated tumors. On the basis of these promising results, we examined the role of Sec62 in cancer cell biology in vitro. Cell migration assays with lung and thyroid cancer cells showed distinct stimulation of migration in SEC62-overexpressing cells and inhibition of migration in Sec62-depleted cells. Moreover, we found that SEC62 silencing sensitized the cells to thapsigargin-induced endoplasmic reticulum stress. Thus, our results indicate that SEC62 represents a potential candidate oncogene in the amplified 3q region in cases of non-small cell lung cancer and harbors various functions in cancer cell biology.
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, Saarland University, Homburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Linxweiler
authors.forename: Johannes
authors.initials: J
authors.lastname: Linxweiler
authors.forename: Monika
authors.initials: M
authors.lastname: Barth
authors.forename: Julia
authors.initials: J
authors.lastname: Benedix
authors.forename: Volker
authors.initials: V
authors.lastname: Jung
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Rainer M
authors.initials: RM
authors.lastname: Bohle
authors.forename: Richard
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Markus
authors.initials: M
authors.lastname: Greiner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005784:Gene Amplification / Q000235:genetics*; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D019284:Thapsigargin / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D026901:Membrane Transport Proteins; C487977:PIK3AP1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C103676:SEC62 protein, human; D019284:Thapsigargin; D004250:DNA Topoisomerases, Type II