PEA15 promotes liver metastasis of colorectal cancer by upregulating the ERK/MAPK signaling pathway.

Abstract

Liver metastasis is one of the major causes of death in patients with colorectal cancer, and although treatment has improved recently, the long-term survival rate of patients has not improved significantly. In the present study, we used immunohistochemistry to determine that phosphoprotein enriched in astrocytes-15 kDa (PEA15) was highly expressed in colorectal cancer tissues and liver metastatic cancer tissues. It was also highly expressed in metastatic colorectal cancer patients compared to non-metastatic patients. Through clinicopathological data of patients with liver metastasis of colorectal cancer, we found that high expression of PEA15 was positively correlated with TNM staging, liver metastasis and poor prognosis of colorectal cancer patients. Using confocal immunofluorescence microscopy, western blotting and cell proliferation, migration and invasion assays, we also determined that PEA15 could promote cancer cell proliferation in vitro and in vivo, epithelial mesenchymal transition (EMT) and the characteristics of cancer stem cells in vitro, thus promoting the abilities of invasion and migration. In addition, we revealed that PEA15 promoted the liver metastasis of colorectal cancer cells in a xenograft tumor metastasis model. In addition, concerning the mechanism, we used gene chip analysis to determine that PEA15 upregulated the ERK/MAPK signaling pathway in colorectal cancer cells. Therefore, we concluded that PEA15 may be a potential biomarker for liver metastasis of colorectal cancer therapy. Collectively, PEA15 promoted the development of liver metastasis of colorectal cancer through the ERK/MAPK signaling pathway.