?3GnT8 Promotes Gastric Cancer Invasion by Regulating the Glycosylation of CD147.

ABSTRACT: ?1, 3-N-acetylglucosminyltransferase 8(?3GnT8) synthesizes a unique cabohydrate structure known as polylactosamine, and plays a vital role in progression of various human cancer types. However, its involvement in gastric cancer remains unclear. In this study, we analyzed the expression and clinical significance of ?3GnT8 by Western blot in 6 paired fresh gastric cancer tissues, noncancerous tissues and immunohistochemistry on 110 paraffin-embedded slices. ?3GnT8 was found to be over-expressed in gastric cancer tissues, which correlated with lymph node metastasis and TNM stage. Forced the expression of ?3GnT8 promoted migration and invasion of gastric cancer cells, whereas ?3GnT8 knockdown led to the opposite results. Further studies showed that the regulated ?3GnT8 could convert the heterogeneous N-glycosylated forms of CD147 and change the polylactosamine structures carried on CD147. In addition, our data suggested the annexin A2 (ANXA2) to be an essential interaction partner of ?3GnT8 during the process of CD147 glycosylation. Collectively, these results provide a novel molecular mechanism for ?3GnT8 in promotion of gastric cancer invasion and metastasis. Targeting ?3GnT8 could serve as a new strategy for future gastric cancer therapy.

SUBMITTER: Shen L 

PROVIDER: S-EPMC5327381 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature