Loss of polarity protein Par3 is mediated by transcription factor Sp1 in breast cancer
Loss of polarity protein Par3 is mediated by transcription factor Sp1 in breast cancer
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乳腺癌中极性蛋白 Par3 的丢失是由转录因子 Sp1 介导的
DOI：
10.1016/j.bbrc.2021.05.025
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Chen She
中科院分区：
文献类型：
--
作者：
Zhao Yannan;Yao Dingjin;Li Yi;Zhang Si;Tao Zhonghua;Zhang Li;Hu Xichun;Wang Biyun;Chen She
极性蛋白PAR3的缺失促进乳腺癌的发生和转移。乳腺癌中Par3下调的潜在分子机制和相关的预后意义尚不清楚。在这里，我们发现Par3下调与Lumina A亚型乳腺癌的无复发生存期缩短有关。Par3基因敲除促进了乳腺癌细胞的迁移和侵袭。重要的是，我们鉴定了转录因子Sp1结合到PARD3启动子区域并诱导了Par3的表达。Sp1水平低的乳腺癌患者RFS明显恶化，Par3表达水平降低。Par3过表达可部分逆转Sp1基因敲除诱导的细胞迁移和侵袭。总之，Sp1水平的降低通过减少与PARD3启动子的结合，介导了Par3的下调，这与ER+乳腺癌患者的预后不良有关。
Loss of polarity protein Par3 promotes breast cancer tumorigenesis and metastasis. The underlying molecular mechanisms of Par3 down-regulation and related prognostic significance in breast cancer remain unclear. Here, we discovered that Par3 down-regulation was associated with shorter relapse-free survival in Luminal A subtype of breast cancer. Par3 knockdown promoted breast cancer cells migration and invasion. Importantly, we identified that transcription factor Sp1 bound toPARD3promoter region and induced Par3 expression. Breast cancer patients with low Sp1 showed significantly worse RFS and low expression level of Par3. Par3 over-expression partially reversed Sp1 knockdown induced migration and invasion. Together, decreased Sp1 level mediates Par3 down-regulation, which correlated with poor prognosis of ER + breast cancer patients, via reduced binding withPARD3promoter.