Downregulation of L-type amino acid transporter 1 expression inhibits the growth, migration and invasion of gastric cancer cells.

ABSTRACT: Gastric cancer is the second leading cause of cancer-related mortality worldwide. Identifying the molecules that play critical roles in the development of gastric cancer, and clarifying their mechanisms, will contribute to the development of novel molecularly targeted therapeutic drugs. Recently, the large (L)-type amino acid transporter 1 (LAT1), a glycoprotein that transports amino acids through the cell membrane when associated with CD98hc, has been demonstrated to be overexpressed in various types of cancer, and to regulate multiple biological process, including cell growth, migration and invasion. However, the involvement of LAT1 in gastric cancer remains unclear. In the present study, stable gastric cancer cell lines with a LAT1 knockdown were established by transfection of constructs with inserted short (sh) RNAs, in order to clarify the role of LAT1 in gastric caner. A significant decrease in LAT1 expression was observed in the established LAT1-silenced SGC7901 cells compared with the corresponding control cells; however, the expression levels of its partner, CD98hc, were not altered. Furthermore, downregulation of LAT1 expression inhibited the proliferation, migration and invasion of gastric cancer cells. In addition, the decreased expression of LAT1 induced cell cycle arrest in the G1/M phase. These findings suggested that LAT1 may be significant in the progression and metastasis of gastric cancer, and may be developed as a therapeutic target for cancer therapy.

SUBMITTER: Shi L 

PROVIDER: S-EPMC3742819 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature