Caspase-14 is an anti-apoptotic protein targeting apoptosis-inducing factor in lung adenocarcinomas

• Published in: Oncology reports Vol. 26; no. 2; pp. 359 - 369
• Main Authors: FANG, Hsin-Yuan, CHEN, Chih-Yi, HUNG, Min-Fa, HSIAO, Yi-Ting, CHIANG, Ting-Chieh, LIN, Tze-Yi, CHANG, Hui-Wen, CHOW, Kuan-Chih, KO, Wen-Je
• Format: Journal Article
• Language: English
• Published: Athens Spandidos 01.08.2011
• Subjects: Adenocarcinoma - enzymology; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Antibody Specificity; Apoptosis - drug effects; Apoptosis Inducing Factor - genetics; Apoptosis Inducing Factor - metabolism; Apoptosis Regulatory Proteins - metabolism; Biological and medical sciences; Caspase 14 - biosynthesis; Caspase 14 - immunology; Caspase 14 - metabolism; Cell Line, Tumor; Cisplatin - pharmacology; Cohort Studies; Female; HeLa Cells; Humans; Immunohistochemistry; Lung Neoplasms - enzymology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Sequence Data; Neoplasm Recurrence, Local - enzymology; Pneumology; Reverse Transcriptase Polymerase Chain Reaction; Survival Rate; Transfection; Tumors; Tumors of the respiratory system and mediastinum; Antineoplastic agent; anti-apoptosis; Targeting; Lung cancer; Cysteine endopeptidases; caspase-14; Bronchopulmonary adenocarcinoma; Cancerology; Bronchus disease; Apoptosis inducing factor; Platinum II Complexes; Lung disease; Enzyme; Respiratory disease; cisplatin resistance; lung adenocarcinoma; Caspase; Malignant tumor; Cisplatin; Protein; Resistance; Peptidases; Alkylating agent; Antiapoptotic agent; Cell death; Hydrolases; apoptosis-inducing factor; Cancer; Apoptosis
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2011.1292

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.