Insufficient microwave ablation-induced promotion of distant metastasis is suppressed by β-catenin pathway inhibition in breast cancer.
Insufficient microwave ablation-induced promotion of distant metastasis is suppressed by β-catenin pathway inhibition in breast cancer.
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乳腺癌中β-连环蛋白通路抑制作用抑制了微波消融不充分引起的远处转移促进
DOI：
10.18632/oncotarget.22859
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发表时间：
2017-12-29
期刊：
影响因子：
--
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Kong P;Pan H;Yu M;Chen L;Ge H;Zhu J;Ma G;Li L;Ding Q;Zhou W;Wang S
微波消融是一种热消融，是治疗乳腺癌的一种有效方法。然而，仍然可以检测到残留的乳腺癌。热消融后残留乳腺癌的生物学特性尚不清楚。以37℃、42℃、45℃、47℃、50℃处理乳腺癌细胞10分钟，以37℃为对照组。MWA不足在体内外通过下调E-钙粘蛋白、上调波形蛋白和N-钙粘蛋白的表达，诱导残留乳腺癌的EMT样改变。我们首次报道了体内MWA不足可促进残留乳腺癌的远处转移。通过siRNA降低β-catenin的表达，可以减少热处理诱导的乳腺癌细胞的EMT样表型，并增强其迁移能力。此外，β-连环蛋白通路的特异性抑制剂ICG001可以抑制MWA裸鼠乳腺癌模型中残留肿瘤的转移和远处转移。综上所述，我们的结果表明，不足的MWA通过激活β-连环蛋白信号通路促进残留乳腺癌的EMT，从而增强残留乳腺癌的远处转移。此外，初步验证了ICG001抑制残留乳腺癌增强转移的有效性。
Microwave ablation (MWA), a thermal ablation, is an effective treatment for breast cancer. However, residual breast cancer is still detected. The biological characteristics of residual breast cancer after thermal ablation remain unknown. To mimic insufficient MWA in vitro, breast cancer cells were treated at 37°C, 42°C, 45°C, 47°C and 50°C for 10 mins, the 37°C as control group. Insufficient MWA induced EMT-like changes of residual breast cancer by down-regulation of E-cadherin and up-regulation of vimentin and N-cadherin in vitro and in vivo. For the first time, we reported insufficient MWA promoted distant metastasis of residual breast cancer in vivo. Reduced β-catenin expression by siRNA diminished the EMT-like phenotype and enhanced migration capability induced by heat treatment in breast cancer cells. Moreover, ICG001, a special inhibitor of β-catenin pathway, depressed EMT of residual tumor and distant metastasis in an insufficient MWA nude mice model of breast cancer. In conclusion, our results demonstrate that insufficient MWA promotes EMT of residual breast cancer by activating β-catenin signal pathway, resulting in enhanced distant metastasis of residual breast cancer. In addition, the effectiveness of ICG001 in suppressing enhanced metastasis of residual breast cancer is preliminarily validated.
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影响因子：
64.5
作者：
Scheel C;Eaton EN;Li SH;Chaffer CL;Reinhardt F;Kah KJ;Bell G;Guo W;Rubin J;Richardson AL;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
19.7
作者：
Ahmed, Muneeb;Kumar, Gaurav;Goldberg, S. Nahum
通讯作者：
Goldberg, S. Nahum
DOI：
10.1073/pnas.060025397
发表时间：
2000-04-11
影响因子：
11.1
作者：
Lin, SY;Xia, WY;Hung, MC
通讯作者：
Hung, MC
影响因子：
6.6
作者：
Obara, Koichi;Matsumoto, Nobuyuki;Itoh, Fumio
通讯作者：
Itoh, Fumio
影响因子：
5.4
作者：
Pan, Hong;Zhou, Wenbin;Wang, Shui
通讯作者：
Wang, Shui