CD147调控SLUG（SNAIL-2）的机制及其在黑素瘤与乳腺癌侵袭转移过程中的作用

Tumor invasion, metastasis and recurrence are difficult problem in cancer therapy. Most cancer cell in situ have to undergo EMT in invasion and metastasis. SLUG has been identified as one of most important regulator in transcriptional factors and signal pathway proteins modulating invasion and metastasis. In our preliminary study, we screened transcriptional factor array under CD147 deregulated situation. The transcriptional activity of SLUG is regulated by CD147. Western blot results provided evidence CD147 modulating SLUG protein level. Further study based on real-time PCR yield that SLUG transcription level is controlled by CD147. We investigated some downstream effector of SLUG, such as E-cadheren, MMP2, Twist, etc, which were considered as EMT markers. All of the genes we checked were deregulated more or less. In 4 cases of clinical patients samples, we found there are expressional association between CD147 and SLUG. Take it all with our formal data and published references, we made a hypothesis, The effect of CD147 on EMT as well as tumor metastasis and recurrence process possibly mediated by SLUG. The destination of this study is to clarify the mechanism of CD147 modulating SLUG and EMT, to support further study on prognosis of tumor and cancer therapy.

多数原位实体瘤要发生侵袭转移必须要经过上皮-间质细胞(EMT)转化这一阶段，SLUG是调控EMT最为重要的基因之一。前期工作中，以黑素瘤细胞为模型，我们针对CD147进行了转录因子蛋白芯片筛选，发现CD147可以严格调控SLUG的转录活性，WB和Real-time PCR结果显示其调控作用在于影响了SLUG的转录。同时，我们检测了一批SLUG下游的效应因子，同时也是EMT的标志基因，如E-cadheren、MMP2、Twist等，发现CD147对于这些基因都存在程度不同的调控作用。我们检测了4例黑素瘤临床病理样本，发现二者在黑素瘤中的表达具有高度的相关性。因此，我们提出CD147极有可能通过调控SLUG影响了肿瘤细胞EMT的进程，进而影响肿瘤的转移复发。本项目力求鉴定CD147调控SLUG的完整信号通路，阐明CD147调控EMT的机制，为进一步的预后评估和治疗靶点选择打下理论基础。

多数原位实体瘤要发生侵袭转移必须要经过上皮-间质细胞(EMT)转化这一阶段，SLUG 是调控EMT最为重要的基因之一。前期工作中，以黑素瘤细胞为模型，我们针对CD147进行 了转录因子蛋白芯片筛选，发现CD147可以严格调控SLUG的转录活性，WB和Real-time PCR 结果显示其调控作用在于影响了SLUG的转录。同时，我们检测了一批SLUG下游的效应因子 ，同时也是EMT的标志基因，如E-cadheren、MMP2、Twist等，发现CD147对于这些基因都 存在程度不同的调控作用。我们检测了4例黑素瘤临床病理样本，发现二者在黑素瘤中的 表达具有高度的相关性。因此，我们提出CD147极有可能通过调控SLUG影响了肿瘤细胞EMT 的进程，进而影响肿瘤的转移复发。本项目力求鉴定CD147调控SLUG的完整信号通路，阐 明CD147调控EMT的机制，为进一步的预后评估和治疗靶点选择打下理论基础