Xu Tao, Zhou Mingliang, Peng Lipan, Kong Shuai, Miao Ruizheng, Shi Yulong, Sheng Hongguang, Li Leping
Department of Gastrointestinal Surgery, Provincial Hospital Affiliated to Shandong University Jinan, Shandong, China.
Int J Clin Exp Pathol. 2014 Oct 15;7(11):7432-41. eCollection 2014.
Colorectal cancer (CRC) is one of the most common cancers in the world. CD147, a transmembrane protein, has been reported to be correlated with various cancers. In this study, we aimed to investigate the mechanism of CD147 in regulating drug resistance, cell invasion and epithelial-to-mesenchymal transition (EMT) in CRC cells. qRT-PCR and western blotting were used to evaluated the expression of CD147 in 40 CRC cases and 4 cell lines. Increased expression of CD147 at both mRNA and protein levels was found in CRC samples, and the level of CD147 was correlated with lymph node metastasis. CD147 overexpression increased the 5-Fluorouracil (5-FU) resistance, enhanced the invasion and EMT of CRC cells by regulating EMT markers and MMPs. Adverse results were obtained in CD147 knockdown CRC cell line. Further investigation revealed that CD147 activated MAPK/ERK pathway, ERK inhibitor U0126 suppressed the CD147-induced cell invasion, migration and MMP-2, MMP-9 expression. Taken together, our study indicates that CD147 promotes the 5-FU resistance, and MAPK/ERK signaling pathway is involved in CD147-promoted invasion and EMT of CRC cells.
结直肠癌(CRC)是世界上最常见的癌症之一。CD147是一种跨膜蛋白,据报道与多种癌症相关。在本研究中,我们旨在探讨CD147在调节CRC细胞耐药性、细胞侵袭和上皮-间质转化(EMT)中的机制。采用qRT-PCR和蛋白质印迹法评估40例CRC病例和4种细胞系中CD147的表达。在CRC样本中发现CD147在mRNA和蛋白质水平均表达增加,且CD147水平与淋巴结转移相关。CD147过表达增加了5-氟尿嘧啶(5-FU)耐药性,通过调节EMT标志物和基质金属蛋白酶增强了CRC细胞的侵袭和EMT。在CD147敲低的CRC细胞系中获得了相反的结果。进一步研究表明,CD147激活了MAPK/ERK通路,ERK抑制剂U0126抑制了CD147诱导的细胞侵袭、迁移以及MMP-2、MMP-9的表达。综上所述,我们的研究表明CD147促进5-FU耐药,且MAPK/ERK信号通路参与了CD147促进的CRC细胞侵袭和EMT。