| 抄録 |
目的: We evaluate the role of intracellular CD24 in the control of pancreatic ductal adenocarcinoma (PDAC) cell invasion and metastasis.方法: We examined the knockdown effects of CD24 on cell motility and invasion, using in vitro assays and in vivo orthotopic tumor challenge. Subsequently, we utilized proteomics analysis to identify binding partners of intracellular CD24. Those we identified G3BP, a downstream effector protein of Ras signaling with RNase activity. We immunoprecipitated G3BP-RNA complexes from PDAC cell lysates, and performed cDNA microarray analysis of bound transcripts, which identified G3BP target mRNAs in the complexes.結果: Knockdown of CD24 increases retroperitoneal invasion and liver metastasis of PDAC cells in an orthotopic xenograft model. Intracellular CD24 binds to G3BP in cytoplasmic stress granules that regulate mRNA stability and translation. At cell protrusions, G3BP binds and degrades BART, an mRNA also in complex with CD24, whose function has not been clearly elucidated. We show that intracellular CD24 inhibits the specific endoribonuclease activity of G3BP for BART mRNA in stress granules, and so BART protein expression is also observed in the lamellipodial-like protrusions of migrating cells. We further show that up-regulation of BART expression by intracellular CD24 inhibits cell invasion. まとめ: Our results imply that surface CD24 may play a role in the inhibition of cell invasion and metastasis, and that intracellular CD24 inhibits invasiveness and metastasis through its influence on the post-transcriptional regulation of BART mRNA levels via G3BP RNase activity. |
