Metastasis-associated in colon cancer-1 upregulation predicts a poor prognosis of gastric cancer, and promotes tumor cell proliferation and invasion

摘要

Metastasis-associated in colon cancer-1 (MACC1) is a newly identified oncogene, and little is known about its role in gastric cancer (GC). Our study was performed to investigate whether MACC1 influences the prognosis of GC patients and to explore the potential mechanisms involved. MACC1 expression was verified to be higher in GC tissues than in adjacent nontumorous tissues by Western blotting. A retrospective analysis of 361 GC patients (Stages I-IV) revealed that higher MACC1 expression was associated with more advanced disease, more frequent postoperative recurrence, more metastases and a higher mortality rate. The disease-free survival of Stage I-III patients and overall survival of Stage-IV patients were significantly worse when their tumors showed high MACC1 expression. To investigate the underlying mechanisms, MACC1 overexpression and downregulation were established in two GC cell lines (BGC-823 and MKN-28 cells). MACC1 overexpression significantly accelerated tumor growth and facilitated metastasis in athymic mice. MACC1 also promoted the proliferation, migration and invasion of both GC cell lines. Moreover, gastric MACC1 mRNA expression levels were significantly correlated with markers of the epithelial-to-mesenchymal transition (EMT) in patients with GC. MACC1 overexpression upregulated mesenchymal-epithelial transition factor and induced changes to markers of EMT, whereas silencing of MACC1 reversed all these changes. These findings provide some novel insights into the role of MACC1, a gene that contributes to a poor prognosis of GC by promoting tumor cell proliferation and invasion as well as the EMT. What's new? The oncogene metastasis-associated in colon cancer-1 (MACC1) has been reported to promote the progression of colorectal and pancreatic cancers, though whether it has a similar role in gastric cancer has remained uncertain. Here, MACC1 is demonstrated to be closely associated with progression, recurrence, metastasis, and mortality of gastric cancer in patients. It was also found to stimulate growth and metastasis of gastric tumors in athymic mice, to promote proliferation and invasion in gastric cancer cells, and to modulate the epithelial-to-mesenchymal transition. The findings suggest that MACC1 may be a novel prognostic indicator for gastric cancer.