STC2 promotes the epithelial-mesenchymal transition of colorectal cancer cells through AKT-ERK signaling pathways.
STC2 promotes the epithelial-mesenchymal transition of colorectal cancer cells through AKT-ERK signaling pathways.
复制标题
DOI：
10.18632/oncotarget.12147
复制
发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Liang S
中科院分区：
文献类型：
--
作者：
Chen B;Zeng X;He Y;Wang X;Liang Z;Liu J;Zhang P;Zhu H;Xu N;Liang S
STC2蛋白参与多种癌症的发生和发展。目前尚不清楚STC2如何调控上皮-间充质转化(EMT)过程和结直肠癌(CRC)的发展。在这里，我们系统地研究了STC2激活的EMT和结直肠癌细胞体外迁移的早期发生，以及STC2与结直肠癌发展和患者生存的临床相关性。与正常上皮NCM460细胞相比，EMT细胞和结直肠癌细胞中STC2的分泌和表达水平均显著增加。EMT细胞的条件培养液刺激上皮细胞和结肠癌细胞获得EMT特性。在体外，STC2过表达促进了结直肠癌细胞的生长和细胞的迁移，在小鼠结直肠癌-异种移植模型中，STC2促进了肿瘤的生长。与EMT标志物表达变化相对应，无论是在NCM460细胞中还是在外源STC2蛋白诱导下，PERK、PACK、PI3K和RAS等几个关键信号通路分子在NCM460细胞中均显著增加。然而，阻断AKT-ERK信号通路可减弱STC2激活的EMT过程。此外，在77例临床肿瘤组织和血清中也证实了STC2的高表达，肿瘤组织和血清中STC2的高表达与肿瘤的病理分期和患者的预后有关。总之，STC2通过激活ERK/MEK和PI3K/AKT信号通路促进结直肠癌的发生和EMT进展。STC2蛋白也是判断结直肠癌诊断和预后的潜在肿瘤标志物。
The STC2 protein involves in carcinogenesis and progression of many cancers. It remains unclear how STC2 regulates the epithelial-mesenchymal transition (EMT) process and colorectal cancer (CRC) development. Here we systematically investigated STC2-activated early occurrence of EMT and CRC cell migration in vitro, clinical associations of STC2 with CRC development and patient survival. The secretion and expression level of STC2 were both greatly increased in EMT cells and CRC cells compared with the normal epithelial NCM460 cells. And the conditioned media from EMT cells stimulated epithelia and colon cancer cells to obtain EMT characteristics. STC2 overexpression promoted CRC cell growth and cell migration in vitro, and STC2 enhanced tumor growth in a mouse CRC-xenograft model. Corresponding to EMT marker expression changes, several critical signaling pathway molecules including pERK, pAKT, PI3K and Ras were remarkably increased either in NCM460 cells transfected with STC2 plasmids or in cells induced with exogenous STC2 protein. However blocking AKT-ERK signaling pathways attenuated STC2-activated EMT process. Furthermore the elevated STC2 expressions were also confirmed in 77 clinical tumor tissues and sera from CRC patients, and the increased STC2 in tumor tissues and sera correlated with tumor pathologic stage and poor survival for CRC patients. In conclusion, STC2 promotes CRC tumorigenesis and EMT progression through activating ERK/MEK and PI3K/AKT signaling pathways. STC2 protein is also a potential tumor biomarker for CRC diagnosis and prognosis.