Activation of IRE1α-XBP1 pathway induces cell proliferation and invasion in colorectal carcinoma
Autor: | Lu Min, Chun Jin, Wanle Hu, Chenguo Zheng, Zhao Jin, Chang-bao Liu, Nian-zhao Chen |
---|---|
Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Male X-Box Binding Protein 1 China XBP1 Epithelial-Mesenchymal Transition Biophysics Regulatory Factor X Transcription Factors Biology Protein Serine-Threonine Kinases Biochemistry 03 medical and health sciences Cyclin D1 Endoribonucleases Biomarkers Tumor Prevalence Gene silencing Humans Neoplasm Invasiveness Epithelial–mesenchymal transition Molecular Biology Cell Proliferation Cell growth Cell Biology Survival Analysis digestive system diseases Cell biology DNA-Binding Proteins 030104 developmental biology Tumor progression Ectopic expression Female Signal transduction Colorectal Neoplasms Signal Transduction Transcription Factors |
Zdroj: | Biochemical and biophysical research communications. 470(1) |
ISSN: | 1090-2104 |
Popis: | Cell proliferation and tumor metastasis are considered as the main reasons for death in colorectal carcinoma (CRC). IRE1α-XBP1 pathway is the most conserved UPR pathways, which are activated during ER stress caused by the accumulation of unfolded or misfolded protein in the lumen of ER. Here, we demonstrated the critical role of IRE1α-XBP1 pathway and underlying molecular mechanism in cell proliferation and tumor metastasis in CRC. By the use of tissue microarray analysis of samples from 119 patients with CRC, IRE1α was determined to be an independent predictor of overall survival as higher expression of IRE1α in CRC patients showed lower survival rates (p = 0.0041). RNA interference and ectopic expression of IRE1α were applied to determine the molecular effects of IRE1α in CRC cells. The silencing of IRE1α inhibited the proliferation and blocked the invasion of CRC cells in vitro, while ectopic expression of IRE1α in turn promoted cell proliferation and invasion. IRE1α-XBP1 pathway regulated the mitosis of CRC cells through the directly binding of XBP1s to Cyclin D1 promoter to activate Cyclin D1 expression. Our results reveal that IRE1α-XBP1 pathway plays an important role in tumor progression and epithelial-to-mesenchymal transition (EMT), and IRE1α could be employed as a novel prognostic marker and a promising therapeutic target for CRC. |
Databáze: | OpenAIRE |
Externí odkaz: |