STX2 promotes colorectal cancer metastasis through a positive feedback loop that activates the NF-κB pathway
| Autor: | Shu-Yang Wang, Hong-Li Jiao, Hong-Hai Xu, Tingting Li, Zhi-Yuan Xiao, Li Liang, Shan-Shan Liu, Jun-Feng Qiu, Wenting Liao, Ya-Ping Ye, Yanqing Ding, Wen-Ting Wei, Yali Zhao, Yong-Xia Wang, Jiaxin Bi |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Cancer Research Colorectal cancer Syntaxin 1 Metastasis chemistry.chemical_compound fluids and secretions 0302 clinical medicine hemic and lymphatic diseases Medicine Neoplasm Metastasis Promoter Regions Genetic Feedback Physiological lcsh:Cytology NF-kappa B Middle Aged Up-Regulation Gene Expression Regulation Neoplastic Treatment Outcome 030220 oncology & carcinogenesis Female Tumor necrosis factor alpha Signal transduction Colorectal Neoplasms Signal Transduction Immunology Down-Regulation Mice Nude Article 03 medical and health sciences Cellular and Molecular Neuroscience Downregulation and upregulation Cell Line Tumor Animals Humans lcsh:QH573-671 TNF Receptor-Associated Factor 6 Oncogene business.industry NF-κB Cell Biology bacterial infections and mycoses medicine.disease digestive system diseases 030104 developmental biology chemistry Cancer research bacteria business Chromatin immunoprecipitation |
| Zdroj: | Cell Death and Disease, Vol 9, Iss 6, Pp 1-14 (2018) Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-018-0675-x |
| Popis: | Metastatic progression is the main contributor to the poor prognosis of colorectal cancer (CRC). Thus, identifying the determinants of CRC metastasis will be of great significance. Based on our previous bioinformatics analysis, Syntaxin2 (STX2) may be upregulated and correlated with the poor prognosis of CRC patients. In this study, we found that STX2 expression was associated with CRC invasion and metastasis and poor patient survival. Gain- and loss-of-function analyses demonstrated that STX2 functioned as a key oncogene by promoting CRC invasion and metastasis. Mechanistically, STX2 selectively interacted with tumor necrosis factor receptor-associated factor 6 (TRAF6) and activated the nuclear transcription factor-κB (NF-κB) signaling pathway. Furthermore, chromatin immunoprecipitation (ChIP) analysis revealed that NF-κB directly bound to the STX2 promoter and drove STX2 transcription. Therefore, STX2 activated the NF-κB pathway, and in turn, NF-κB increased STX2 expression, forming a positive signaling loop that eventually promoted CRC metastasis. Collectively, our results reveal STX2 as a crucial modulator of the aggressive CRC phenotype and highlight STX2 as a potential prognostic biomarker and therapeutic target for combating CRC metastasis. |
| Databáze: | OpenAIRE |
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