Identifying apoptosis-evasion proteins/pathways in human hepatoma cells via induction of cellular hormesis by UV irradiation
| Autor: | Shao-Jung Lo, Ying-Ching Chen, Chiung-Liang Liu, Jung-Ru He, Hui-Yu Huang, Chih-Yun Hsu, Sen-Yung Hsieh |
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| Rok vydání: | 2009 |
| Předmět: |
Proteomics
Carcinoma Hepatocellular Proteome Ultraviolet Rays Immunoblotting Molecular Sequence Data Apoptosis Biology medicine.disease_cause Biochemistry RNA interference Cell Line Tumor Prohibitins medicine Gene silencing Humans Electrophoresis Gel Two-Dimensional Amino Acid Sequence Gene knockdown Analysis of Variance Liver Neoplasms Reproducibility of Results Tumor Protein Translationally-Controlled 1 General Chemistry Cell biology Neoplasm Proteins Cell culture Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization RNA Interference Signal transduction Carcinogenesis Apoptosis Regulatory Proteins Signal Transduction |
| Zdroj: | Journal of proteome research. 8(8) |
| ISSN: | 1535-3893 |
| Popis: | Evading apoptosis is pivotal in both of carcinogenesis and resistance to anticancer therapy. We investigated the molecules and pathways of apoptosis evasion in human hepatoma cells by irradiating hepatoma cells with optimized UV (so-called "hormetic responses"). Proteins and pathways related to hormetic responses were identified via proteomic approaches followed by reconstruction of function-networks. Of the 2326 defined protein spots, 42 distinct proteins significantly changed their expression. Eleven hormetic response proteins (HINT1, PHB, CTSD, ANXA1, LGASL1, TPT1, NPM, PRDX2, UCHL1, CERK, and C1QBP) were involved in 5 death-regulatory pathways, including the p53-dependent apoptotic pathway, protein ubiquinization, cellular redox, calcium-mediated signaling pathway, and sphingomyelin-metabolism pathway. Knockdown of HINT1 expression via RNA interference increased tumor cell resistance to apoptosis induction, while silencing NPM, UCHL1, or CERK greatly sensitized tumor cells to apoptosis induction. In conclusion, NPM, UCHL1, and CERK act as apoptosis-evasion proteins that may serve as therapeutic targets for hepatoma. Silencing their expression would increase therapeutic efficacy, thereby reducing the corresponding doses and side-effects of anticancer therapy. This model of induction of cellular hormetic responses to identify apoptosis-evasion molecules/pathways via proteomic approaches can be applied to other modalities of anticancer therapy. |
| Databáze: | OpenAIRE |
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