Upregulation of CD147 promotes cell invasion, epithelial-to-mesenchymal transition and activates MAPK/ERK signaling pathway in colorectal cancer

• Published in: International journal of clinical and experimental pathology Vol. 7; no. 11; pp. 7432 - 7441
• Main Authors: Xu, Tao, Zhou, Mingliang, Peng, Lipan, Kong, Shuai, Miao, Ruizheng, Shi, Yulong, Sheng, Hongguang, Li, Leping
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 01.01.2014
• Subjects: Basigin - genetics; Basigin - metabolism; Cell Line, Tumor; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Female; Fluorouracil - pharmacology; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Male; MAP Kinase Signaling System; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Original; Up-Regulation; colorectal cancer; 5-FU resistance; invasion; CD147; EMT; MAPK/ERK pathway
• ISSN: 1936-2625

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.