Wen Feng, Liu Yongmei, Wang Wei, Li Meng, Guo Fuchun, Sang Yaxiong, Qin Qing, Wang Yongsheng, Li Qiu
The Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, University of Sichuan, Sichuan, China.
State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, University of Sichuan, Sichuan, China.
Oncotarget. 2016 Feb 16;7(7):7761-72. doi: 10.18632/oncotarget.6844.
Toll-like receptors (TLRs)/NF-κB activation stimulated by lipopolysaccharide (LPS) was associated with diverse biological response in colon cancer, but the underlying mechanism was largely unknown. In the current study, we reported cell proliferation was elevated in adenomatous polyposis coli (APC) mutated- and APC knockdown cell lines, while the proliferation was inhibited in APC wild-type cell lines. Besides, in vivo experiments showed that LPS promoted APC knockdown tumor growth while inhibited proliferation of APC wild type. Further study confirmed that activation of TLRs/NF-κB signaling pathway by LPS cross regulated with APC/GSK-3β/β-catenin pathway, which were depend on APC status of cell lines. Taken together, APC genotypes play a key role in LPS induced different colon cancer biological response by cross-regulating β-catenin and NF-κB, which may provide a novel strategy for carcinogenesis prevention.
脂多糖（LPS）刺激的Toll样受体（TLRs）/核因子κB（NF-κB）激活与结肠癌的多种生物学反应相关，但其潜在机制尚不清楚。在本研究中，我们发现腺瘤性息肉病大肠杆菌（APC）突变和APC敲低的细胞系中细胞增殖增加，而在APC野生型细胞系中增殖受到抑制。此外，体内实验表明，LPS促进APC敲低肿瘤的生长，同时抑制APC野生型肿瘤的增殖。进一步研究证实，LPS激活的TLRs/NF-κB信号通路与APC/糖原合成酶激酶-3β（GSK-3β）/β-连环蛋白通路相互交叉调节，这取决于细胞系的APC状态。综上所述，APC基因型通过交叉调节β-连环蛋白和NF-κB，在LPS诱导的不同结肠癌生物学反应中起关键作用，这可能为癌症预防提供一种新策略。
