Effects of legumain as a potential prognostic factor on gastric cancers

Li, Na; Liu, Qiaoling; Su, Qi; Wei, Chongyang; Liu, Bin; Wang, Jian-Yong; Bao, Gang; Yan, Fei; Yu, Ying; Peng, Binbin; Qiu, Jing; Yan, Xiao; Zhang, Sheng; Guo, Fang

doi:10.1007/s12032-013-0621-9

Cited by 56 publications

(47 citation statements)

References 23 publications

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“…Under physiological conditions, legumain is primarily expressed in kidney tubuli and contributes to renal tubular reabsorption 20,21 . Results of several studies have indicated that legumain expression is upregulated in a variety of different solid tumour types to a level that is positively correlated with the potential of malignancy [22][23][24] . As well as tumour cells themselves, several other cell types in the tumour-associated microenvironment have also been reported to express high levels of legumain, especially TAMs 14,16 .…”

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confidence: 99%

Legumain protease-activated TAT-liposome cargo for targeting tumours and their microenvironment

et al. 2014

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Specific targeting and cellular internalization are key properties for carriers of antitumor therapeutic agents. Here, we develop a drug carrier through the attachment of substrate of endoprotease legumain, alanine-alanine-asparagine (AAN), to cell-penetrating peptides (TAT, trans-activating factor). The addition of the AAN moiety to the fourth lysine in the TAT creates a branched peptide moiety, which leads to a decrease in the transmembrane transport capacity of TAT by 72.65%. Legumain efficiently catalyses the release of TAT-liposome from the AAN-TAT-liposome and thereby recovers the penetrating capacity of TAT. Doxorubicin carried by the AAN-TAT-liposome led to an increase in the tumoricidal effect of doxorubicin and a reduction in its systemic adverse effects in comparison with doxorubicin carried by a control delivery system. Thus, the specific targeting and high efficiency of this delivery platform offers a novel approach to limit the toxicity of anticancer agents as well as increasing their efficacy in cancer therapy.

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confidence: 99%

Legumain protease-activated TAT-liposome cargo for targeting tumours and their microenvironment

et al. 2014

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“…This is similar to some previous reports. 10 This result might suggest AEP would be a prognostic biomarker in EOC. And based on this hypothesis, we detected that the high expression of AEP could enhance the ability of SKOV3ip cells progression both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 87%

“…11,13,21,22 AEP has recently captured the attention of researchers since some reports have identified that it is expressed higher in many solid tumor tissues compared with normal tissues. 9,10 Moreover, some studies have reported that AEP was related to tumor cell proliferation. 8,23 And blocking of AEP with antibody was reported to inhibit tumor progression and metastasis.…”

Section: Discussionmentioning

confidence: 99%

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The expression of asparaginyl endopeptidase promotes growth potential in epithelial ovarian cancer

Zhu

Tang

2017

Cancer Biology & Therapy

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Epithelial ovarian cancer (EOC) is the most common and lethal cancer-related death among females in the world. Asparaginyl endopeptidase (AEP) is a member of C13 family peptidases and expressed in the extracellular matrix and tumor cells. The aim of this article is to explore the function of asparaginyl endopeptidase in epithelial ovarian cancer. The expression of AEP was examined in 20 EOC samples, 3 EOC metastasis samples, 6 fallopian tube metastasis samples, 4 peritoneum metastasis samples and 20 benign ovarian tumor samples by immunohistochemistry. The expression of AEP was also evaluated in serum and ascites of EOC patients by elisa. And we used a lentiviral vector to overexpress AEP in human epithelial ovarian cancer cell lines SKOV3ip and detected the function of AEP-SKOV3ip cells both in vitro and in vivo. The growth of AEP-SKOV3ip cells was observed by MTT, migration and tube formation assays in vitro. Additionally, the subcutaneous mice model was used to identify the tumor growth and metastasis in vivo. Mice tumors were stained for CD31 to determine the microvessel density (MVD). We demonstrated that AEP was highly expressed in the EOC patient tissues and ascites. The AEP transfected SKOV3ip cells could both promote tumor growth in vitro and in vivo. The MVD in AEP-SKOV3ip group was higher than that in NC-SKOV3ip group. Therefore, our results demonstrated that AEP could induce EOC growth and progressionboth in vitro and in vivo.

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“…AEP overexpression was observed in some solid tumors, such as breast cancer, colon cancer, lung cancer, and acute lymphoblastic leukemia [9–14]. The expression of AEP was higher in gastric cancer than that in the normal gastric mucosa, and AEP was an independent prognostic factor of gastric cancer [15–16]. However, the mechanism by which AEP promotes invasion and metastasis in gastric cancer remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Asparaginyl endopeptidase promotes the invasion and metastasis of gastric cancer through modulating epithelial-to-mesenchymal transition

Cui

Wang

et al. 2016

Oncotarget

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Asparaginyl endopeptidase (AEP) is a lysosomal protease often overexpressed in gastric cancer. AEP was expressed higher in peritoneal metastatic loci than in primary gastric cancer. Then we overexpressed AEP or knocked it down with a lentiviral vector in gastric cancer cell lines and detected the cell cycle arrest and the changes of the invasive and metastatic ability in vitro and in vivo. When AEP was knocked-down, the proliferative, invasive and metastatic capacity of gastric cancer cells were inhibited, and the population of sub-G1 cells increased. AEP knockdown led to significant decrease of expression of transcription factor Twist and the mesenchymal markers N-cadherin, ß-catenin and Vimentin and to increased expression of epithelial marker E-cadherin. These results showed that AEP could promote invasion and metastasis by modulating EMT. We used phosphorylation-specific antibody microarrays to investigate the mechanism how AEP promotes gastric cancer invasion and metastasis, and found that the phosphorylation level of AKT and MAPK signaling pathways was decreased significantly if AEP was knocked-down. Therefore, AKT and MAPK signaling pathways took part in the modulation.

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Effects of legumain as a potential prognostic factor on gastric cancers

Cited by 56 publications

References 23 publications

Legumain protease-activated TAT-liposome cargo for targeting tumours and their microenvironment

Legumain protease-activated TAT-liposome cargo for targeting tumours and their microenvironment

The expression of asparaginyl endopeptidase promotes growth potential in epithelial ovarian cancer

Asparaginyl endopeptidase promotes the invasion and metastasis of gastric cancer through modulating epithelial-to-mesenchymal transition

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