PA28β regulates cell invasion of gastric cancer via modulating the expression of chloride intracellular channel 1.

PA28β is a subunit of proteasome activator PA28. Previous study suggests that PA28β is involved in the invasiveness and metastasis of gastric adenocarcinoma (GA), however, the mechanism is not fully understood. In the present study, we showed that invasive abilities of gastric cancer cells were enhanced when PA28β being down-regulated, and were inhibited when PA28β being overexpressed. To explore the possible mechanism of PA28β associated elevated invasiveness, the protein profiles of PA28β knock down and parental negative control gastric cancer cells were compared using proteomics approach. The results revealed that there were 43 proteins were differentially expressed, among them, chloride intracellular channel 1 (CLIC1) was significantly up-regulated and selected for further functional study. Down-regulation of CLIC1 by RNA interference was able to markedly inhibit cell invasion of PA28β knock down gastric carcinoma cells. In addition, an inverse correlation between PA28β and CLIC1 expressions was also verified in GA tissue samples, suggesting that knockdown of PA28β could enhance tumor invasion and metastasis, at least in part, through up-regulation of CLIC1. Our results provide novel insight into the mechanisms of PA28β related invasiveness and metastasis of GA, and suggest new alternative approaches for GA treatment.

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