HERPUD1 promotes ovarian cancer cell survival by sustaining autophagy and inhibit apoptosis via PI3K/AKT/mTOR and p38 MAPK signaling pathways.

HERPUD1 is an important early marker of endoplasmic reticulum stress (ERS) and is involved in the ubiquitination and degradation of several unfolded proteins. However, its role in tumorigenesis is seldom studied, and its role in ovarian cancer is unclear. Lewis y antigen is a tumor-associated sugar antigen that acts as an 'antenna' on the cell surface to receive signals from both inside and outside the cell.

miR-5193, regulated by FUT1, suppresses proliferation and migration of ovarian cancer cells by targeting TRIM11.

Ovarian cancer is the most lethal gynecological malignancy worldwide. A better understanding of the pathogenesis of ovarian cancer may help to improve the overall survival. Our previous studies have demonstrated that alpha-(1,2)-fucosyltransferase 1 (FUT1) is an oncogenic glycogene in ovarian cancer.

TGF-β1 fucosylation enhances the autophagy and mitophagy via PI3K/Akt and Ras-Raf-MEK-ERK in ovarian carcinoma.

Transforming growth factor-β, a cell secretion factor of the TGF-β superfamily, is involved in the regulation of cell proliferation, differentiation, cytoskeleton formation, migration, invasion and other biological behaviors. Autophagy and mitophagy play an important role in tumor progression by regulating self-digestion, and degradation and reuse of cells and mitochondria. In this study, changes in autophagy and mitophagy processes in ovarian cancer cells under TGF-β1 treatment were detected via Western blot and immunofluorescence, as well as the role of fucosylation modification.

Interaction of HE4 and ANXA2 exists in various malignant cells-HE4-ANXA2-MMP2 protein complex promotes cell migration.

Background: The interaction between human epididymis protein 4 (HE4) and annexin A2 (Annexin A2) has been found in ovarian cancer. However, it is dimness whether the interaction exists in other malignant tumors.

Methods: Real-time PCR, western blotting and immunocytochemistry were used to detect mRNA and proteins expression.

TMEFF1 overexpression and its mechanism for tumor promotion in ovarian cancer.

Background: Transmembrane protein with epidermal growth factor-like and two follistatin-like domains 1 (TMEFF1) has an anticarcinogenic effect in brain tumors. However, little is known about the role of TMEFF1 in epithelial ovarian cancer (EOC).

Materials And Methods: TMEFF1 expression in EOC was detected by immunohistochemistry; its relationship with clinical pathological parameters and its influence on prognosis were analyzed.

Lewis y antigen promotes p27 degradation by regulating ubiquitin-proteasome activity.

As a tumor-associated carbohydrate antigen, elevated expression of Lewis y promotes the malignant behaviors of tumor cells. Although our preliminary study showed that the increased expression of Lewis y antigen decreased the expression of cell cycle inhibitor protein p27, the relevant mechanism remains unclear. Autophagy and the ubiquitin-proteasome system are two main ways of intracellular protein degradation, whose abnormal activities are closely associated with progression of malignant tumors.

c-Fos mediates α1, 2-fucosyltransferase 1 and Lewis y expression in response to TGF-β1 in ovarian cancer.

FUT1 is a key rate-limiting enzyme in the synthesis of Lewis y, a membrane-associated carbohydrate antigen. The aberrant upregulation of FUT1 and Lewis y antigen is related to proliferation, invasion and prognosis in malignant epithelial tumors. A c-Fos/activator protein-1 (AP-1) binding site was found in the FUT1 promoter.

Lewis(y) antigen promotes the progression of epithelial ovarian cancer by stimulating MUC1 expression.

MUC1 is a type I transmembrane glycoprotein and is overexpressed in various epithelial tumor tissues. Some researchers have demonstrated that the glycosylation status of MUC1 can affect MUC1-mediated tumor growth and cell differentiation. In our previous study, we proved that the abilities of cell proliferation, adhesion, invasion and metastasis, and drug resistance were enhanced in ovarian cancer cells stably expressing Lewis(y).

Gene expression profile analysis in response to α1,2-fucosyl transferase (FUT1) gene transfection in epithelial ovarian carcinoma cells.

The aim of this study was to identify differentially expressed genes (DEGs) in response to α1,2-fucosyl transferase (FUT1) gene transfection in epithelial ovarian cancer cells. Human whole-genome oligonucleotide microarrays were used to determine whether gene expression profile may differentiate the epithelial ovarian cell line Caov-3 transfected with FUT1 from the empty plasmid-transfected cells. Quantitative real-time PCR and immunohistochemical staining validated the microarray results.

Lewis Y antigen modified CD47 is an independent risk factor for poor prognosis and promotes early ovarian cancer metastasis.

CD47 is a membrane receptor that belongs to the immunoglobulin superfamily and plays an important role in the mechanisms of tumor immune escape. CD47 participates in tumor immune escape by combining with SIRPα to reduce the phagocytic activity of macrophages. There are six potential N-glycosylation sites on CD47, and glycosylation is known to be necessary for its membrane localization.

Lewis y enhances CAM-DR in ovarian cancer cells by activating the FAK signaling pathway and upregulating Bcl-2/Bcl-XL expression.

Oligosaccharides on the surface of adhesion molecules may contribute to the process of CAM-DR. To investigate the role of the Lewis y antigen in this process, we established a cell adhesion model mediated by the integrin α5β1-FN interaction in the ovarian cancer cell line, RMG-1-hFUT, which highly expresses Lewis y by transfection with α1,2-fucosyltransferase into RMG-1 cells. Our results indicate that the rates of carboplatin-induced apoptosis and necrosis are reduced in FN-adhered tumor cells, and carboplatin resistance is significantly decreased in the presence of anti-Lewis y antibody.

The expression and correlation between the transcription factor FOXP1 and estrogen receptors in epithelial ovarian cancer.

Background: Estrogen plays an important role in the progression of ovarian cancer in humans. FOXP1 belongs to the forkhead/winged-helix transcription factor family, and previous research indicated that FOXP1 functioned as a tumor suppressor gene. FOXP1 may be similar to FOXA1 and is closely related to steroid hormone receptors, but the relationship between FOXP1 and ER currently remains unclear.

Human epididymis protein 4 in association with Annexin II promotes invasion and metastasis of ovarian cancer cells.

Background: The objective of the present study was to identify human epididymis protein 4 (HE4) interacting proteins and explore the mechanisms underlying their effect on ovarian cancer cell invasion and metastasis.

Methods: HE4 interacting proteins were identified by mass spectrometry and validated by co-immunoprecipitation and pull-down assays. The scratch test, the Transwell assay and animal experiments were used to assess the invasive and metastatic abilities of ovarian cancer cells before and after transfection and HE4 protein treatment.

c-Jun transcriptionally regulates alpha 1, 2-fucosyltransferase 1 (FUT1) in ovarian cancer.

Alpha 1, 2-fucosyltransferase (FUT 1/2) is a rate-limiting enzyme that catalyzes the synthesis of Lewis y, a cell membrane-associated carbohydrate antigen. In human ovarian cancer, the upregulated expression of FUT1 and Lewis y is associated with advanced pathological stages and involved in cell proliferation, migration and invasion. However, the mechanism underlying the upregulation of FUT1 is largely unknown.

Overexpression of Lewis y antigen promotes human epididymis protein 4-mediated invasion and metastasis of ovarian cancer cells.

To study Human epididymis protein 4 (HE4) surface fucosylation and to determine the effects and significance of Lewis y antigen on HE4-mediated invasion and metastasis of ovarian cancer cells, we investigated four types of ovarian cancer cells and found that six fucosylated antigens (Lewis y, Lewis x, Lewis a, Lewis b, sLewis a, and sLewis x) were identified on HE4 in ovarian cancer cells. Moreover, modification of the type II sugar chain (Lewis y, Lewis x, and sLewis x) was significantly higher than the type I sugar chain (Lewis a, Lewis b, sLewis a) of the lactose series. To confirm the effects of Lewis y antigen on HE4-mediated invasion and metastasis of ovarian cancer cells, the CaoV-3 cells with high Lewis y antigen on the HE4 surface and ES-2 cells, with high Lewis x antigen but low Lewis y antigen, were investigated.

Expression of CD147 and Lewis y antigen in ovarian cancer and their relationship to drug resistance.

The purpose of this study was to investigate the relationship between the expression of CD147 and Lewis y antigen in epithelial ovarian carcinoma tissues and resistance to chemotherapeutic drugs, and its underlying clinical significance, and to analyze the correlation between the expression of CD147 and Lewis y antigen. Ninety-two ovarian cancer patients were divided into a chemotherapeutic-drug-resistant group (34 patients) and a drug-sensitive group (58 patients). Immunohistochemical assays were used to measure CD147, and Lewis y antigen to investigate their correlation with chemotherapy resistance.

Beclin 1 expression in ovarian tissues and its effects on ovarian cancer prognosis.

Beclin 1 is an autophagy-associated protein involved in apoptosis and drug resistance, as well as various malignancies. We investigated the expression of Beclin 1 protein in ovarian epithelial tissues and correlated it with the prognosis of ovarian cancer. Beclin 1 protein expression was determined using immunohistochemistry in 148 patients with ovarian epithelial cancer, 26 with ovarian borderline tumor, 25 with benign ovarian tumor, and 30 with normal ovarian tissue.

Co-expression of Lewis y antigen with human epididymis protein 4 in ovarian epithelial carcinoma.

Objective: The main aims of this study were to explore the molecular structural relationship between Human epididymis protein 4 (HE4) and Lewis y antigen by determining their expression patterns and clinical significance in ovarian epithelial carcinoma.

Methods: The structural relationship between HE4 and Lewis y antigen was examined using immunoprecipitation and confocal laser scanning microscopy. HE4 and Lewis y were detected in tissues from malignant (53 cases), borderline (27 cases), benign (15 cases) and normal ovarian tissues (15 cases) using immunohistochemical analysis.

Expression of Lewis y antigen and integrin αv, β3 in ovarian cancer and their relationship with chemotherapeutic drug resistance.

Objective: This study investigates the expression of Lewis y antigen, integrin αv, β3 in epithelial ovarian cancer tissues. We further evaluate the relationship between their expression and chemotherapy resistance of ovarian cancer and its possible clinical significance.

Methods: Tissues of 92 patients with ovarian cancer meeting the inclusion criteria with complete follow-up data were enrolled and divided into chemotherapy resistant group and sensitive group.

High expression of Lewis y antigen and CD44 is correlated with resistance to chemotherapy in epithelial ovarian cancers.

Objectives: To measure Lewis y antigen and CD44 antigen expression in epithelial ovarian carcinoma and to correlate the levels of these antigens with clinical response to chemotherapy.

Methods: The study cases included 34 cases of ovarian carcinoma with resistance to chemotherapeutic drugs, 6 partially drug-sensitive cases, and 52 drug-sensitive cases (92 total).

Results: The rates of expression of Lewis y antigen and CD44 antigen were significantly greater in the drug-resistant group than that in the partially-sensitive or sensitive groups.

Elevated levels of Lewis y and integrin α5β1 correlate with chemotherapeutic drug resistance in epithelial ovarian carcinoma.

Objective: To measure Lewis y and integrin α(5)β(1) expression in epithelial ovarian carcinoma and to correlate the levels of these molecules with ovarian carcinoma chemotherapy and prognosis.

Methods: The study population included 34 ovarian carcinoma patients with chemotherapeutic drug-resistance, six partially drug-sensitive cases, and 52 drug-sensitive cases (92 total). Immunochemistry was used to determine expression of Lewis y antigen and integrin α(5)β(1) in ovarian carcinoma tissues, and correlation of these molecules with chemotherapy resistance was further investigated, Multi-factor logistic regression analysis was applied to investigate: age, surgical stage, grade, subtype of patient cases, metastasis of lymph nodes, residual tumor size, expression levels of Lewis y antigen and integrin α(5)β(1) correlation with ovarian carcinoma chemotherapy resistance.

Autophagy-independent enhancing effects of Beclin 1 on cytotoxicity of ovarian cancer cells mediated by proteasome inhibitors.

Background: The ubiquitin-proteasome system and macroautophagy (hereafter referred to autophagy) are two complementary pathways for protein degradation. Emerging evidence suggests that proteasome inhibition might be a promising approach for tumor therapy. Accumulating data suggest that autophagy is activated as a compensatory mechanism upon proteasome activity is impaired.

Expression of high-risk HPV DNA and CK19 in pelvic lymph nodes in stage Ia-IIa cervical cancer and their clinical value.

The aim of this study was to investigate the detection rate and methods of micrometastases in early-stage cervical cancer by detecting the expression of high-risk HPV DNA and CK19 in pelvic lymph nodes. A total of 104 lymph nodes with/without pathologically confirmed metastases, from 28 patients with early-stage cervical cancer, were included for detection of high-risk HPV DNA and CK19 expression using in situ hybridization and immunohistochemistry, respectively. The detection rate of high-risk HPV DNA and CK19 in lymph nodes in patients with pathologically-confirmed lymph node metastases was higher compared to that in lymph nodes in patients without pathologically-confirmed lymph node metastases (P<0.

Lewis y regulate cell cycle related factors in ovarian carcinoma cell RMG-I in vitro via ERK and Akt signaling pathways.

Objective: To investigate the effect of Lewis y overexpression on the expression of proliferation-related factors in ovarian cancer cells.

Methods: mRNA levels of cyclins, CDKs, and CKIs were measured in cells before and after transfection with the α1,2-fucosyltransferase gene by real-time PCR, and protein levels of cyclins, CDKs and CKIs were determined in cells before and after gene transfection by Western blot.

Results: Lewis y overexpression led to an increase in both mRNA and protein expression levels of cyclin A, cyclin D1 and cyclin E in ovarian cancer cells, decrease in both mRNA and protein expression levels of p16 and p21, and decrease of p27 at only the protein expression level without change in its mRNA level.