BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation
BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation
复制标题
DOI：
10.1007/s13277-015-3681-y
复制
发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Min, Byung Wook
中科院分区：
文献类型：
--
作者：
Kim, Bo Ram;Oh, Sang Cheul;Min, Byung Wook
骨形态发生蛋白(BMPs)参与了多种癌症的转移和肿瘤发生。然而，目前还不清楚BMP-2如何在这些癌症的发生和发展中起作用。在这里，我们研究了BMP-2在结肠癌干细胞(CSC)从结肠癌细胞发展中的作用。我们还检测了BMP-2对人结肠癌细胞系HCT-116和SW620的CSC发育和上皮-间充质转化(EMT)的影响。我们发现BMP-2在无血清的情况下促进了结肠癌细胞球体的形成。此外，BMP-2诱导的球体显示出干细胞标志(CD133+和EpCAM+)的上调和耐药性的增加，这是CSCs的特征。重要的是，EMT激活剂p-Smad1/5、Snail和N-cadherin在球体细胞中的表达增加，提示BMP-2信号可能导致CSC自我更新和EMT。此外，siRNA介导的信号转导和转录激活因子3(STAT3)在HCT-116细胞中的下调逆转了BMP-2诱导的EMT和干细胞的形成。综上所述，我们的结果提示，BMP-2诱导的STAT3介导的结肠癌细胞转移需要EMT和/或CSC标志物的改变。
Bone morphogenetic proteins (BMPs) have been involved in metastatic progression and tumorigenesis of many cancer types. However, it remains unclear how BMP-2 contributes to the initiation and development of these cancers. Here, we investigated the role of BMP-2 in colon cancer stem cell (CSC) development from colon cancer cells. We also determined the effects of BMP-2 on CSC development and epithelial-mesenchymal transition (EMT) in human colon cancer cell lines HCT-116 and SW620. We found that BMP-2 enhanced sphere formation of colon cancer cells without serum. Also, BMP-2-induced spheres displayed up-regulation of stemness markers (CD133+ and EpCAM+) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activators p-Smad1/5 and Snail and N-cadherin was increased in the spheres' cells, indicating that BMP-2 signaling might result in CSC self-renewal and EMT. Furthermore, siRNA-mediated knockdown of signal transducer and activator of transcription 3 (STAT3) in HCT-116 cells reversed BMP-2-induced EMT and stem cell formation. Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.