title: Caspase-14 is an anti-apoptotic protein targeting apoptosis-inducing factor in lung adenocarcinomas.
abstract: Using apoptosis-inducing factor protein as bait in a yeast hybrid assay to screen protein libraries, we identified three proteins that interacted with apoptosis-inducing factor: human homolog of yeast Rad23 protein A (hHR23A), microsomal glutathione S-transferase and caspase-14 (casp-14). In this study, we investigated the expression and function of casp-14 in lung adenocarcinomas (LADC). Our results showed that monoclonal antibodies were specific to casp-14, and that casp-14 was highly expressed in LADC. Casp-14 overexpression correlated with tumor stage, cell differentiation and lymphovascular involvement, suggesting that casp-14 was associated with tumor cell growth and metastatic potential. In vitro, casp-14 interacted with apoptosis-inducing factor, and silencing of casp-14 expression reduced cisplatin resistance. Our data suggest that casp-14 is an anti-apoptotic protein targeting apoptosis-inducing factor and increases cisplatin resistance in LADC cells.
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University School of Medicine, Taipei, Taiwan, ROC.
authors.forename: Hsin-Yuan
authors.initials: HY
authors.lastname: Fang
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Min-Fa
authors.initials: MF
authors.lastname: Hung
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Hsiao
authors.forename: Ting-Chieh
authors.initials: TC
authors.lastname: Chiang
authors.forename: Tze-Yi
authors.initials: TY
authors.lastname: Lin
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Kuan-Chih
authors.initials: KC
authors.lastname: Chow
authors.forename: Wen-Je
authors.initials: WJ
authors.lastname: Ko
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D053456:Caspase 14 / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D015331:Cohort Studies; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009364:Neoplasm Recurrence, Local / Q000201:enzymology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D051033:Apoptosis Inducing Factor; D051017:Apoptosis Regulatory Proteins; D053456:Caspase 14; D002945:Cisplatin