Thioredoxin-Like Protein 2 Is Overexpressed in Colon Cancer and Promotes Cancer Cell Metastasis by Interaction with Ran
| Autor: | Zhenxiong Liu, Kai Li, Yuanyuan Lu, Antonio Miranda-Vizuete, Gui Ren, Yi Zhou, Yongquan Shi, Yongzhan Nie, Xin Wang, Yan Pan, Xuegang Guo, Bin Feng, Kaichun Wu, Xiaodi Zhao, Ting Li, Daiming Fan, Guanhong Luo |
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| Přispěvatelé: | National Natural Science Foundation of China, Ministry of Science and Technology of the People's Republic of China |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Physiology Colorectal cancer Clinical Biochemistry Gene Expression Biology Biochemistry Metastasis Cell Line Tumor Gene Order medicine Humans Protein Isoforms Neoplasm Metastasis Molecular Biology Aged Neoplasm Staging Proportional Hazards Models General Environmental Science Gene knockdown Cell Biology Middle Aged medicine.disease Molecular biology Matrix Metalloproteinases Nucleoside-diphosphate kinase Alternative Splicing ran GTP-Binding Protein Cell culture Gene Knockdown Techniques Colonic Neoplasms Cancer cell General Earth and Planetary Sciences Female Thioredoxin Signal transduction Carrier Proteins Proto-Oncogene Proteins c-akt Original Research Communication Protein Binding Signal Transduction |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1557-7716 1523-0864 |
| Popis: | Lu, Yuanyuan et al. [Aims] Our previous work identified thioredoxin-like protein 2 (Txl-2) as the target of the monoclonal antibody MC3 associated with colon cancer, but its underlying mechanisms remain poorly understood. Txl-2, a novel thioredoxin (Trx) and nucleoside diphosphate kinase family member, is alternatively spliced and gives rise to three different Txl-2 isoforms. In this study, Txl-2 expression in colon cancer, differential functions for Txl-2 isoforms in cell invasion and metastasis, and the downstream signaling were investigated. [Results] Txl-2 expression was elevated in colon cancer tissues compared to normal colonic tissues, with a high correlation between the histological grade and prognosis. Knockdown of Txl-2 expression significantly inhibited cancer cell motility, and the invasive and metastatic abilities of colon cancer cells. Interestingly, Txl-2 isoforms showed differential effects on cancer cell invasion and metastasis. Cell invasion and metastasis were significantly promoted by Txl-2b but inhibited by Txl-2c, while no obvious effect was observed for Txl-2a. Furthermore, a direct interaction was identified between Txl-2b and Ran, a Ras-related protein, by yeast two-hybrid assay and coimmunoprecipitation. PI3K pathway was found to be a major pathway mediating Txl-2b induced tumor invasion and metastasis. [Innovation] The current study provides a novel biomarker and target molecule for the diagnosis and treatment of colon cancer and provides a novel paradigm to understand how alternative splicing functions in human cancer. [Conclusion] Our findings demonstrate an elevated Txl-2 expression in colon cancer and that Txl-2b promotes cell invasion and metastasis through interaction with Ran and PI3K signaling pathway. © 2013, Mary Ann Liebert, Inc. This work was supported by grants from National Key Basic Research and Development Program (2010CB529300, 2009CB521805, 2010CB529306) and National Science Foundation of China (NSF: 81201929, 30971337, 81272650). |
| Databáze: | OpenAIRE |
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