HMGA1 Promotes Hepatic Metastasis of Colorectal Cancer by Inducing Expression of Glucose Transporter 3 (GLUT3).

BACKGROUND Colorectal cancer (CRC) is one of the most common cancers worldwide, and more than half of CRC patients have CRC liver metastasis (CRCLM). Mounting evidence indicates that high mobility group protein A1(HMGA1) is overexpressed in many cancer types, but its role in CRCLM has been obscure. MATERIAL AND METHODS Using immunohistochemistry, we assessed the expression of HMGA1 in 73 patients with CRCLM, and compared HMGA1 mRNA in 17 pairs of CRCs, CRCLM tissues, and normal liver tissues. The clinical significance of HMGA1 was evaluated by analyzing its correlation with the clinicopathological factors and overall survival (OS) rates. The function of HMGA1 in CRC invasion was investigated and the underlying mechanism of HMGA1-induced invasion was explored with in vitro experiments. RESULTS In CRCLMs, the high-HMGA1 and low-HMGA1 patients accounted for 53.42% and 46.58% of all patients, respectively. High HMGA1 expression in CRCLM was significantly associated with low OS rates. In vitro experiments demonstrated that HMGA1 promoted glucose transporter 3 (GLUT3) transcription and expression in CRC cells. GLUT3 was required in HMGA1-involved invasion, and GLUT3 expression was associated with poor prognosis of CRCLM. CONCLUSIONS High HMGA1 and GLUT3 expression in CRCLM was significantly correlated with poor prognosis of CRCLM. HMGA1 promoted CRC invasion by elevating GLUT3 transcription and expression.