当前位置：
X-MOL 学术
›
Cell Death Dis.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
TLR5: A prognostic and monitoring indicator for triple-negative breast cancer.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-12-18 , DOI: 10.1038/s41419-019-2187-8 Dai Shi 1 , Shanshan Zhao 1 , Wen Jiang 1 , Chao Zhang 1 , Ting Liang 1 , Guihua Hou 1
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-12-18 , DOI: 10.1038/s41419-019-2187-8 Dai Shi 1 , Shanshan Zhao 1 , Wen Jiang 1 , Chao Zhang 1 , Ting Liang 1 , Guihua Hou 1
Affiliation
|
A novel, highly selective biomarker is urgently needed to predict and monitor triple-negative breast cancer (TNBC) because targeting molecules are not currently available. Although associated with various malignant tumors, the role of toll-like receptor 5 (TLR5) in TNBC remains uncertain. We aimed to define the effects of TLR5 in TNBC to determine whether it could serve as a prognostic and monitoring indicator for TNBC. We established TNBC cell line 4T1 with low TLR5 expression (GFP tag; TLR5- 4T1) and with normal TLR5 expression (GFP tag; TLR5+ 4T1) using lentivirus-shRNA-TLR5 knockdown transfection and negative lentivirus transfection, respectively. Detected by western blot and qPCR, we found knockdown of TLR5 resulted in decreased expression of TLR5 and E-cadherin and increased expression of N-cadherin, vimentin, fibronectin, TRAF6, SOX2, and Twist1, which were related to EMT (epithelial-mesenchymal transition). In addition, downregulation of TLR5 increased the invasion and migration of 4T1 cells in vitro, which were investigated by CCK-8 and wound healing, as well as transwell assay and colony formation. Furthermore, the metastatic ability of TLR5- 4T1 cells to the lungs was also increased compared to TLR5+ 4T1 cells in vivo. To verify the effect of TLR5 as a monitor indicator, mice bearing TLR5+ and TLR5- 4T1 tumors injected with 125I-anti-TLR5 mAb or isotype 125I-IgG were assessed by whole body phosphor-autoradiography and fluorescence imaging in vivo. Phosphor-autoradiography of model mice revealed early tumors at 6 days after inoculation with TLR5+ 4T1, but not TLR5- 4T1 cells. Intratumoral accumulation of radioactivity positively correlated with TLR5 expression, and fluorescence imaging in vivo revealed both TLR5+ and TLR5- 4T1 tumors. Our results suggested that downregulation of TLR5 in TNBC increased tumor invasiveness and EMT expression via TRAF6 and SOX2 pathway and TLR5 could serve as a prognostic and monitoring indicator for TLR5-positive tumors.
中文翻译：
TLR5：三阴性乳腺癌的预后和监测指标。
由于靶向分子目前尚不可用，因此迫切需要一种新颖的，高度选择性的生物标志物来预测和监测三阴性乳腺癌（TNBC）。尽管与各种恶性肿瘤有关，但Toll样受体5（TLR5）在TNBC中的作用仍不确定。我们旨在定义TLR5在TNBC中的作用，以确定其是否可以作为TNBC的预后指标和监测指标。我们分别使用慢病毒-shRNA-TLR5敲低转染和阴性慢病毒转染建立了具有低TLR5表达（GFP标签； TLR5-4T1）和具有正常TLR5表达（GFP标签； TLR5 + 4T1）的TNBC细胞系4T1。通过Western印迹和qPCR检测，我们发现TLR5的敲低导致TLR5和E-钙粘蛋白的表达降低，而N-钙粘蛋白，波形蛋白，纤连蛋白，TRAF6，SOX2的表达增加，和Twist1，它们与EMT（上皮-间质转化）有关。此外，TLR5的下调增加了体外4T1细胞的侵袭和迁移，这通过CCK-8和伤口愈合以及transwell分析和集落形成进行了研究。此外，与体内TLR5 + 4T1细胞相比，TLR5- 4T1细胞向肺的转移能力也有所提高。为了验证TLR5作为监测指标的作用，通过全身荧光自显影和体内荧光成像评估了注射了125I-抗TLR5 mAb或同种型125I-IgG的携带TLR5 +和TLR5-4T1肿瘤的小鼠。模型小鼠的荧光放射自显影显示在接种TLR5 + 4T1，但未接种TLR5-4T1细胞后的第6天出现了早期肿瘤。肿瘤内放射性蓄积与TLR5表达呈正相关，体内荧光成像显示TLR5 +和TLR5- 4T1肿瘤。我们的结果表明，TNBC中TLR5的下调通过TRAF6和SOX2途径增加了肿瘤的侵袭性和EMT表达，而TLR5可以作为TLR5阳性肿瘤的预后和监测指标。
更新日期：2019-12-19
中文翻译：
TLR5：三阴性乳腺癌的预后和监测指标。
由于靶向分子目前尚不可用，因此迫切需要一种新颖的，高度选择性的生物标志物来预测和监测三阴性乳腺癌（TNBC）。尽管与各种恶性肿瘤有关，但Toll样受体5（TLR5）在TNBC中的作用仍不确定。我们旨在定义TLR5在TNBC中的作用，以确定其是否可以作为TNBC的预后指标和监测指标。我们分别使用慢病毒-shRNA-TLR5敲低转染和阴性慢病毒转染建立了具有低TLR5表达（GFP标签； TLR5-4T1）和具有正常TLR5表达（GFP标签； TLR5 + 4T1）的TNBC细胞系4T1。通过Western印迹和qPCR检测，我们发现TLR5的敲低导致TLR5和E-钙粘蛋白的表达降低，而N-钙粘蛋白，波形蛋白，纤连蛋白，TRAF6，SOX2的表达增加，和Twist1，它们与EMT（上皮-间质转化）有关。此外，TLR5的下调增加了体外4T1细胞的侵袭和迁移，这通过CCK-8和伤口愈合以及transwell分析和集落形成进行了研究。此外，与体内TLR5 + 4T1细胞相比，TLR5- 4T1细胞向肺的转移能力也有所提高。为了验证TLR5作为监测指标的作用，通过全身荧光自显影和体内荧光成像评估了注射了125I-抗TLR5 mAb或同种型125I-IgG的携带TLR5 +和TLR5-4T1肿瘤的小鼠。模型小鼠的荧光放射自显影显示在接种TLR5 + 4T1，但未接种TLR5-4T1细胞后的第6天出现了早期肿瘤。肿瘤内放射性蓄积与TLR5表达呈正相关，体内荧光成像显示TLR5 +和TLR5- 4T1肿瘤。我们的结果表明，TNBC中TLR5的下调通过TRAF6和SOX2途径增加了肿瘤的侵袭性和EMT表达，而TLR5可以作为TLR5阳性肿瘤的预后和监测指标。
京公网安备 11010802027423号