Our study elucidates a novel mechanism of AEP regulation and an alternative oncogenic pathway for TRAF6 in breast cancer, which suggests that AEP and TRAF6 protein levels may have prognostic implications in breast cancer patients. Thus, AEP may serve as a biomarker as well as new therapeutic target.

Although legumain has been found to be a prognostic factor in both breast cancer and colorectal cancer, its effects on gastric cancer are unknown. In this study, we investigated effects of legumain on gastric cancer and the correlation between legumain expression and prognosis of gastric cancer patients. SGC7901 cells were transduced with legumain cDNA (SGC7901-hLeg) for overexpression of legumain or with legumain shRNA to knock down legumain. In vitro tumor migration was examined by wound healing assay. Furthermore, a tumorigenicity and metastasis mouse model was used to examine legumain function in vivo; asparaginyl endopeptidase inhibitor (AEPI, an inhibitor of legumain) was injected to the mice (i.p.) to evaluate its therapeutic effect. Tissue microarray analysis from 112 gastric cancer patients was performed to evaluate the association between legumain expression and the cumulative survival time. Legumain was highly expressed in gastric cancer patients and some gastric cancer cell lines. Legumain promoted gastric cell migration in vitro and promoted gastric tumor growth and metastasis in vivo, and these effects were reversed by knockdown of legumain with shRNA or treated with AEPI. In gastric cancer clinical samples, legumain expression in tumor was significantly higher than in non-tumor and was negatively associated with the cumulative survival rate. In conclusion, legumain was highly expressed in gastric adenocarcinoma; legumain promoted gastric cancer tumorigenesis and metastasis in vitro and in vivo. Legumain expression in tumor was a poor prognostic factor for gastric cancer patients, and legumain could be a potential target molecule for gastric cancer therapy in clinic.

pH-responsive drug delivery systems have attracted great interest because of their potential use in antitumor therapies. Herein, we report a facile one-pot fabrication of a “host−metal−drug” coordination-bonding system in a mesostructured surfactant/silica hybrid for the pH-responsive drug delivery purpose. The mesostructure has been synthesized by self-assembly of nontoxic and biocompatible F127 Pluronic nonionic surfactant and silica source through a real liquid crystal templating route, in which F127 act as host molecules. Metal ions such as Zn, Cu, and Fe and drugs have been introduced simultaneously into the mesostructure synthesis systems, to form F127−metal−drug coordination-bonding architecture. The cleavage of the coordination bonds that are sensitive to variations in external pH gives rise to the release of the drug under weakly acidic conditions (pH 5.0−6.0). To assist in the release of drugs without significant binding capabilities, a vector has been designed to endow coordinately inert drugs with pH-responsive properties. Furthermore, the pH responsibility has been confirmed by cell assay and in vivo tumor test, opening up new opportunities for the potential application as implants in antitumor therapies.

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