Cheng Guoping, Yang Shifeng, Zhang Gu, Xu Yanxia, Liu Xiaoling, Sun Wenyong, Zhu Liang
Department of Pathology, Zhejiang Cancer Hospital; Cancer Research Institute, Zhejiang Cancer Hospital and Key laboratory Diagnosis and Treatment Technology on Thoracic Oncology of Zhejiang Province.
Department of Pathology, Zhejiang Cancer Hospital.
Onco Targets Ther. 2016 Dec 14;9:7563-7571. doi: 10.2147/OTT.S123986. eCollection 2016.
α-Catenin is an important molecule involved in the maintenance of cell-cell adhesion and a prognostic marker in cancer since its expression is essential for preventing cancer metastasis. However, the mechanism that leads to the downregulation of α-catenin in cancer progression remains unclear. The present study revealed that lipopolysaccharide (LPS)-induced NF-κB signaling activation suppressed α-catenin expression and motility in SW620 colorectal cancer (CRC) cells, using real-time polymerase chain reaction, Western blotting, and transwell migration assays. LPS treatment reduced both the mRNA and protein expression of α-catenin and thereby enhanced cell motility. Conversely, incubating cells with an NF-κB inhibitor disrupted these effects. Furthermore, the ectopic expression of p65 alone mimicked the effects of LPS stimulation. In CRC tissues, the presence of enteric bacterial LPS-related neutrophil-enriched foci was correlated with α-catenin downregulation. Collectively, these findings suggest that LPS-induced NF-κB signaling is related to α-catenin suppression and enhanced cell motility in CRC. Therefore, NF-κB is a novel potential therapeutic target for CRC metastasis.
α-连环蛋白是一种参与维持细胞间黏附的重要分子，也是癌症的一种预后标志物，因为其表达对于预防癌症转移至关重要。然而，在癌症进展过程中导致α-连环蛋白下调的机制仍不清楚。本研究通过实时聚合酶链反应、蛋白质印迹法和Transwell迁移试验表明，脂多糖（LPS）诱导的NF-κB信号激活抑制了SW620结肠直肠癌（CRC）细胞中α-连环蛋白的表达和迁移能力。LPS处理降低了α-连环蛋白的mRNA和蛋白质表达，从而增强了细胞迁移能力。相反，用NF-κB抑制剂处理细胞则消除了这些影响。此外，单独异位表达p65可模拟LPS刺激的效果。在CRC组织中，富含肠道细菌LPS的中性粒细胞聚集灶的存在与α-连环蛋白下调相关。总体而言，这些发现表明，LPS诱导的NF-κB信号与CRC中α-连环蛋白的抑制及细胞迁移能力增强有关。因此，NF-κB是CRC转移的一个新的潜在治疗靶点。
