SLUG and SOX9 Cooperatively Regulate Tumor Initiating Niche Factors in Breast Cancer
SLUG and SOX9 Cooperatively Regulate Tumor Initiating Niche Factors in Breast Cancer
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DOI：
10.1007/s12307-015-0176-8
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发表时间：
2016-04-01
影响因子：
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通讯作者：
Behnam, Babak
中科院分区：
文献类型：
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作者：
Fazilaty, Hassan;Gardaneh, Mossa;Behnam, Babak
肿瘤起始细胞和适当的生态位的存在对于转移定植至关重要。 SLUG 和 SOX9 转录因子在乳腺癌细胞的肿瘤启动能力的诱导和维持中发挥着重要作用。另一方面，Tenascin-C 和 Periostin 是转移生态位中支持乳腺癌肿瘤启动能力的关键因素。在本研究中，检测了 SLUG 和 SOX9 转录因子对 Tenascin-C 和 Periostin 表达的调节作用。 SLUG 和 SOX9 分别在 MCF7 和 MDA-MB-231 细胞中过表达和敲低。这些细胞是小的和高度侵袭性的乳腺癌衍生细胞，被诱导和 shRNA 慢病毒构建体感染。然后，通过实时 PCR 测量细胞中 Tenascin-C 和 Periostin 以及 SLUG 和 SOX9 的表达水平。 SLUG 和 SOX9 的同时过表达显着诱导 Tenascin-C 和 Periostin 表达。 SLUG 和 SOX9 敲低也显着降低了 Tenascin-C 和 Periostin 的表达。在此分析中，Periostin 在上调和下调水平上显示出最大的偏差。这种调节作用可能有助于揭示乳腺癌肿瘤起始能力和转移生态位相关因素之间的串扰。
Presence of tumor initiating cells and a proper niche is essential for metastatic colonization. SLUG and SOX9 transcription factors play essential roles in induction and maintenance of tumor initiating capacity in breast cancer cells. On the other hand, Tenascin-C and Periostin are crucial factors in metastatic niche that support tumor initiating capability in breast cancer. In this study, regulatory effect of SLUG and SOX9 transcription factors on the expression of Tenascin-C and Periostin was examined. SLUG and SOX9 were overexpressed and knocked-down in MCF7 and MDA-MB-231 cells, respectively. The cells as little and highly invasive breast cancer-derived cells were infected by inducing and shRNA lentivirus constructs. Then, Tenascin-C and Periostin as well as SLUG and SOX9 expression levels were measured in the cells via Real-Time PCR. Simultaneous overexpression of SLUG and SOX9 significantly induced Tenascin-C and Periostin expression. SLUG and SOX9 knock-down also significantly reduced the expression of Tenascin-C and Periostin. In this analysis Periostin showed the most deviation in both up- and down-regulation levels. This regulatory effect might shed light to a crosstalk between factors involved in the tumor initiating capacity and metastatic niche of the breast cancer.