MUC20 promotes aggressive phenotypes of epithelial ovarian cancer cells via activation of the integrin β1 pathway

Chen, Chi-Hau; Shyu, Ming‐Kwang; Wang, Shuwei; Chou, Chih-Hsing; Huang, Miao-Juei; Lin, Tzu-Chi; Chen, Syue-Ting; Lin, Ho‐Hsiung; Huang, Min-Chuan

doi:10.1016/j.ygyno.2015.11.025

Cited by 34 publications

(28 citation statements)

References 32 publications

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“…Another study demonstrated that MUC4 is the predominant mucin detected in endometrial adenocarcinoma, with 77.1% of samples being positive (48). MUC20 is also overexpressed in ovarian and endometrial cancer tissues (51,52) and was originally identified in kidney (53). Similarly, MUC17 was shown to be overexpressed in mucinous epithelial ovarian cancer (54).…”

Section: Discussionmentioning

confidence: 99%

Human Three-Dimensional Endometrial Epithelial Cell Model To Study Host Interactions with Vaginal Bacteria and Neisseria gonorrhoeae

et al. 2017

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Colonization of the endometrium by pathogenic bacteria ascending from the lower female reproductive tract (FRT) is associated with many gynecologic and obstetric health complications. To study these host-microbe interactions in vitro, we developed a human three-dimensional (3-D) endometrial epithelial cell (EEC) model using the HEC-1A cell line and the rotating wall vessel (RWV) bioreactor technology. Our model, composed of 3-D EEC aggregates, recapitulates several functional/structural characteristics of human endometrial epithelial tissue, including cell differentiation, the presence of junctional complexes/desmosomes and microvilli, and the production of membrane-associated mucins and Toll-like receptors (TLRs). TLR function was evaluated by exposing the EEC aggregates to viral and bacterial products. Treatment with poly(I·C) and flagellin but not with synthetic lipoprotein (fibroblast-stimulating lipoprotein 1 [FSL-1]) or lipopolysaccharide (LPS) significantly induced proinflammatory mediators in a dose-dependent manner. To simulate ascending infection, we infected EEC aggregates with commensal and pathogenic bacteria: Lactobacillus crispatus, Gardnerella vaginalis, and Neisseria gonorrhoeae. All vaginal microbiota and N. gonorrhoeae efficiently colonized the 3-D surface, localizing to crevices of the EEC model and interacting with multiple adjacent cells simultaneously. However, only infection with pathogenic N. gonorrhoeae and not infection with the other bacteria tested significantly induced proinflammatory mediators and significant ultrastructural changes to the host cells. The latter observation is consistent with clinical findings and illustrated the functional specificity of our system. Additionally, we highlighted the utility of the 3-D EEC model for the study of the pathogenesis of N. gonorrhoeae using a well-characterized ΔpilT mutant. Overall, this study demonstrates that the human 3-D EEC model is a robust tool for studying host-microbe interactions and bacterial pathogenesis in the upper FRT.

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Section: Discussionmentioning

confidence: 99%

Human Three-Dimensional Endometrial Epithelial Cell Model To Study Host Interactions with Vaginal Bacteria and Neisseria gonorrhoeae

et al. 2017

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“…Glycosylation is an enzymatic process that links carbohydrates to molecules, like proteins, lipids, or other sugars, and aberrant glycosylation affects many cellular properties, including cell proliferation, differentiation, transformation, migration, invasion, apoptosis, and immune responses [9–11]. N -glycosylation and O -glycosylation are the two major types of protein glycosylation in mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

GALNT6 expression enhances aggressive phenotypes of ovarian cancer cells by regulating EGFR activity

et al. 2017

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Ovarian cancer is the most lethal of the gynecologic malignancies. N-acetylgalactosaminyltransferase 6 (GALNT6), an enzyme that mediates the initial step of mucin type-O glycosylation, has been reported to regulate mammary carcinogenesis. However, the expression and role of GALNT6 in ovarian cancer are still unclear. Here we showed that high GALNT6 expression correlates with increased recurrence, lymph node metastasis, and chemoresistance in ovarian endometrioid and clear cell carcinomas; and higher GALNT6 levels are significantly associated with poorer patient survivals. GALNT6 knockdown with two independent siRNAs significantly suppressed viability, migration, and invasion of ovarian cancer cells. Using phospho-RTK array and Western blot analyses, we identified EGFR as a critical target of GALNT6. GALNT6 knockdown decreased phosphorylation of EGFR, whereas GALNT6 overexpression increased the phosphorylation. Lectin pull-down assays with Vicia villosa agglutinin (VVA) indicated that GALNT6 was able to modify O-glycans on EGFR. Moreover, the GALNT6-enhanced invasive behavior was significantly reversed by erlotinib, an EGFR inhibitor. Our results suggest that GALNT6 expression is associated with poor prognosis of ovarian cancer and enhances the aggressive behavior of ovarian cancer cells by regulating EGFR activity.

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“…In contrast, a gene‐lncRNA fusion (MUC20_chr3‐ENSG00000236833_chr3) was found to be significantly enriched in PC samples (five samples) than in normal samples (one sample). MUC20 encodes a member of the mucin protein family, which has been reported to play an important role in several cancers such as colorectal and ovarian cancers . ENSG00000236833, a long intervening noncoding RNA, comes from a long region on chromosome 3 which contained five genes or pseudogenes (KIAA0226, FYTTD1, LOC220729, LOC101926986, and LOC100131868) and 1 miRNA (MIR922).…”

Section: Resultsmentioning

confidence: 99%

Network‐based integration of mRNA and miRNA profiles reveals new target genes involved in pancreatic cancer

Lin

Liang

et al. 2018

Molecular Carcinogenesis

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Pancreatic cancer is regarded as the most fatal and aggressive malignancy cancer due to its low 5‐year survival rate and poor prognosis. The approaches of early diagnosis and treatment are limited, which makes it urgent to identify the complex mechanism of pancreatic oncogenesis. In this study, we used RNA‐seq to investigate the transcriptomic (mRNA and miRNA) profiles of pancreatic cancer in paired tumor and normal pancreatic samples from ten patients. More than 1000 differentially expressed genes were identified, nearly half of which were also found to be differentially expressed in the majority of examined patients. Functional enrichment analysis revealed that these genes were significantly enriched in multicellular organismal and metabolic process, secretion, mineral transport, and intercellular communication. In addition, only 24 differentially expressed miRNAs were found, all of which have been reported to be associated with pancreatic cancer. Furthermore, an integrated miRNA‐mRNA interaction network was generated using multiple resources. Based on the calculation of disease correlation scores developed here, several genes present in the largest connected subnetwork, such as albumin, ATPase H+/K+ exchanging alpha polypeptide and carcinoembryonic antigen‐related cell adhesion molecule 1, were considered as novel genes that play important roles in the development of pancreatic cancer. Overall, our data provide new insights into further understanding of key molecular mechanisms underlying pancreatic tumorigenesis.

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MUC20 promotes aggressive phenotypes of epithelial ovarian cancer cells via activation of the integrin β1 pathway

Cited by 34 publications

References 32 publications

Human Three-Dimensional Endometrial Epithelial Cell Model To Study Host Interactions with Vaginal Bacteria and Neisseria gonorrhoeae

Human Three-Dimensional Endometrial Epithelial Cell Model To Study Host Interactions with Vaginal Bacteria and Neisseria gonorrhoeae

GALNT6 expression enhances aggressive phenotypes of ovarian cancer cells by regulating EGFR activity

Network‐based integration of mRNA and miRNA profiles reveals new target genes involved in pancreatic cancer

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