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

Abstract

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.

Cleavage of tropomodulin-3 by asparagine endopeptidase promotes cancer malignancy by actin remodeling and SND1/RhoA signaling

“…Asparagine endopeptidase (AEP), also known as legumain (LGMN), is a lysosomal cysteine proteinase belonging to the C13 family peptidases [ 30 ]. AEP is highly expressed and correlates with poor prognosis and advanced clinical stage in various solid tumors including rectal cancer [ 31 ], breast cancer [ 32 , 33 ], epithelial ovary cancer [ 34 ] and gastric cancer [ 35 ]. Our previous work showed that, after being cleaved at N311, wild-type p53 can be inactivated by AEP, leading to the loss of the p53 tumor suppressor function in GBM [ 36 ].…”

Identification and analysis of long non-coding RNA related miRNA sponge regulatory network in bladder urothelial carcinoma

“…Numerous studies have demonstrated that ion channels play an important role in tumorigenesis and progression, such as inducing neo-angiogenesis [65], apoptosis resistance [66], proliferative potential [67] as well as cell migration and invasiveness [68, 69]. In terms of endopeptidase activity, Zhu et al [70]. demonstrated that asparaginyl endopeptidase (AEP) was highly expressed in tissues and ascites of patients with epithelial ovarian cancer and promoted tumor growth and progression both in vivo and in vitro.…”

Upregulation of LGMNP1 confers radiotherapy resistance in glioblastoma

“…However, it also occurs extracellularly and even translocates to the cytosol and the nucleus. LGMN has also been reported to be associated with the development of a variety of tumor types, including breast cancer, gastric carcinoma, ovarian and colorectal cancer, and it may even serve as a biomarker for such tumors (31)(32)(33)(34). Furthermore, LGMN was indicated to promote the proliferation and invasiveness of prostate cancer cells via the PI3K/AKT signaling pathway (35).…”