NUBPL, A Novel Metastasis-related Gene, Promotes Colorectal Carcinoma Cell Motility by Inducing EMT

Summary

NUBPL is an assembly factor for human mitochondrial complex I, which is the biggest member of mitochondrial respiratory chain. However, the relationship between NUBPL and carcinoma progression remains unknown. In this study, NUBPL was characterized for its role in colorectal cancer (CRC) and the underlying molecular mechanisms. Data (n=197) from Oncomine database revealed that mRNA levels of NUBPL were remarkably overexpressed in CRC tissues compared with normal tissues. In addition, immunohistochemical analysis of 75 pairs of CRC and nontumorous tissues demonstrated that expression level of NUBPL was significantly higher in CRC tissues, and its expression level was positively associated with lymph node metastasis (P=0.028) and advanced staging (P=0.030). NUBPL expression in metastatic lymph node of CRC patients was also detected by immunohistochemical staining and high expression level of NUBPL was observed. Overexpression of NUBPL significantly promoted migration and invasion ability of CRC cell lines SW480 and SW620, whereas knockdown of NUBPL lead to an opposite effect. Our further study found that NUBPL could induce epithelial-mesenchymal transition (EMT), characterized by down-regulation of epithelial markers (E-cadherin) and and up-regulation of mesenchymal markers (N-cadherin and vimentin). Moreover, NUBPL was able to activate extracellular signal-regulated kinase (ERK), which is believed to promote EMT and tumor metastasis. Inhibition of ERK suppressed the NUBPL-induced changes in EMT and cell motility. These data showed that NUBPL plays a vital role in CRC migration and invasion by inducing EMT and activating ERK. It might be a novel therapeutic target for CRC.

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