Abstract
Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Invasion and metastasis are the main cause of mortality in most CRC patients. Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6) regulated glycosylation, which is frequently altered in cancers, and play an important role in cancer development. However, the role of GALNT6 in CRC remains unknown. To investigate the role of GALNT6 in CRC, first we studied correlation of GALNT6 expression levels with outcomes of CRC patients and found CRC patients with higher expression of GALNT6 had a better overall survival than those with lower expression. In addition, GALNT6 expression were significantly associated with tumor size, histological differentiation and lymph node metastasis. In vitro, GALNT6 overexpression dramatically inhibited cellular colony formation, migration, and invasion, and promoted the apoptosis of CRC cells. In vivo, CRC with GALNT6 overexpression showed reduced pulmonary metastasis in recipient mice compared with the controls. GALNT6 expression was significantly increased in SW480 and SW1116 cells cultured in hypoxic condition, and decreased in HT29 and LOVO cells with oxidative stress. Affimetrix microarray analysis showed that GALNT6 overexpression induced 279 genes up-regulated and 215 genes down-regulated in CRC. GALNT6 overexpression dramatically suppressed AKT and activated CD28 signaling pathway in CRC. AKT rescue experiment found that AKT was involved in GALNT6-induced CRC cell migration and invasion. In conclusion, our results first suggest that GALNT6 plays an important role in development and progression of CRC as a tumor suppressor gene.