The Pivotal Roles of the Epithelial Membrane Protein Family in Cancer Invasiveness and Metastasis

Amin, Mohammad Khusni Bin Ahmat; Shimizu, Akio; Ogita, Hisakazu

doi:10.3390/cancers11111620

Cited by 37 publications

(24 citation statements)

References 129 publications

(151 reference statements)

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“…7 The members of the epithelial membrane protein (EMPs) family, including EMP1, EMP2, and EMP3, have four putative transmembrane domains with approximately 160 amino acid residues. 8 EMPs are encoded by the peripheral myelin protein 22 kDa (PMP22) gene family, and involved in tumor cell migration, growth, and differentiation. 9 EMP1 is also known as CL-40, tumor-associated membrane protein (TMP), B4B.…”

Section: Introductionmentioning

confidence: 99%

<p>EMP1 Promotes the Proliferation and Invasion of Ovarian Cancer Cells Through Activating the MAPK Pathway</p>

Liu¹,

Ding²,

Nie³

et al. 2020

OTT

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Introduction: Epithelial membrane protein 1 (EMP1), a member of the EMP family, is overexpressed in a large number of tumors and is thought to be a cellular connexin on the cell membrane and is involved in proliferation, invasion, metastasis of tumor cells, and epithelial-mesenchymal transition (EMT). Nevertheless, its biomedical function in ovarian cancer is still unclear. Methods: EMP1 was detected in ovarian cancer cell lines by whole transcriptome resequencing. The mRNA of EMP1 was examined by qRT-PCR. The relationship between expression of EMP1 and clinical classification, metastasis, and shortened survival time in ovarian cancer specimens was analysed by immunohistochemical (IHC). The mechanism of EMP1 enhanced proliferation and invasion of ovarian cancer cells was determined by siRNA interference, colony formation, migration and invasion experiments, and Western blot. Results: EMP1 was up-regulated in ovarian cancer cell lines and ovarian cancer tissues in comparison with non-cancerous ovarian specimens. High expression of EMP1 in ovarian cancer specimens was obviously related to high clinical classification, metastasis, and shortened survival time. High expressed EMP1 facilitates cell proliferation, invasion and EMT in ovarian cancer cells. Over-expressed EMP1 increased the protein levels of RAS/ RAF/MAPK/c-JUN. Conclusion: Over-expressed EMP1 in ovarian cancer promotes tumor cell proliferation, invasion, and EMT by the MAPK signaling pathway.

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Section: Introductionmentioning

confidence: 99%

<p>EMP1 Promotes the Proliferation and Invasion of Ovarian Cancer Cells Through Activating the MAPK Pathway</p>

Liu¹,

Ding²,

Nie³

et al. 2020

OTT

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“…Decorin ( DCN ), a crucial player in physiological angiogenesis, shows an obvious inhibitory function in angiogenesis within the tumor microenvironment [ 35 ]; for example, microinvasive carcinoma of the cervix displayed lower DCN expression than premalignant lesions, as evidenced by immunohistochemistry [ 36 ]. There have also been a lot of contradictory data about the role of EMP1 , epithelial membrane protein 1 (summarized in [ 37 ]); nevertheless, anti-migratory function of EMP1 in nasopharyngeal cancer cells [ 38 ] and its downregulation upon oral dysplasia progression to oral squamous cell carcinoma [ 39 ] have been documented; in addition, the mechanism for anti-lymphangiogenic effect of EMP1 through downregulation of VEGFC expression was proposed [ 38 ]. Epiregulin ( EREG ) considered as a hub gene in squamous cervical carcinoma and other gynecological tumors [ 40 ] has been reported to undergo silencing in certain types of carcinoma [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

“…There have also been a lot of contradictory data about the role of EMP1, epithelial membrane protein 1 (summarized in [37]); nevertheless, anti-migratory function of EMP1 in nasopharyngeal cancer cells [38] and its downregulation upon oral dysplasia progression to oral squamous cell carcinoma [39] have been documented; in addition, the mechanism for anti-lymphangiogenic effect of EMP1 through downregulation of VEGFC expression was proposed [38]. Epiregulin (EREG) considered as a hub gene in squamous cervical carcinoma and other gynecological tumors [40] has been reported to undergo silencing in certain types of carcinoma [41].…”

Section: Differential Gene Expression Analysismentioning

confidence: 99%

Markers of Angiogenesis, Lymphangiogenesis, and Epithelial–Mesenchymal Transition (Plasticity) in CIN and Early Invasive Carcinoma of the Cervix: Exploring Putative Molecular Mechanisms Involved in Early Tumor Invasion

Kurmyshkina

Ковчур

Schegoleva

et al. 2020

IJMS

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The establishment of a proangiogenic phenotype and epithelial-to-mesenchymal transition (EMT) are considered as critical events that promote the induction of invasive growth in epithelial tumors, and stimulation of lymphangiogenesis is believed to confer the capacity for early dissemination to cancer cells. Recent research has revealed substantial interdependence between these processes at the molecular level as they rely on common signaling networks. Of great interest are the molecular mechanisms of (lymph-)angiogenesis and EMT associated with the earliest stages of transition from intraepithelial development to invasive growth, as they could provide the source of potentially valuable tools for targeting tumor metastasis. However, in the case of early-stage cervical cancer, the players of (lymph-)angiogenesis and EMT processes still remain substantially uncharacterized. In this study, we used RNA sequencing to compare transcriptomes of HPV(+) preinvasive neoplastic lesions and early-stage invasive carcinoma of the cervix and to identify (lymph-)angiogenesis- and EMT-related genes and pathways that may underlie early acquisition of invasive phenotype and metastatic properties by cervical cancer cells. Second, we applied flow cytometric analysis to evaluate the expression of three key lymphangiogenesis/EMT markers (VEGFR3, MET, and SLUG) in epithelial cells derived from enzymatically treated tissue specimens. Overall, among 201 differentially expressed genes, a considerable number of (lymph-)angiogenesis and EMT regulatory factors were identified, including genes encoding cytokines, growth factor receptors, transcription factors, and adhesion molecules. Pathway analysis confirmed enrichment for angiogenesis, epithelial differentiation, and cell guidance pathways at transition from intraepithelial neoplasia to invasive carcinoma and suggested immune-regulatory/inflammatory pathways to be implicated in initiation of invasive growth of cervical cancer. Flow cytometry showed cell phenotype-specific expression pattern for VEGFR3, MET, and SLUG and revealed correlation with the amount of tumor-infiltrating lymphocytes at the early stages of cervical cancer progression. Taken together, these results extend our understanding of driving forces of angiogenesis and metastasis in HPV-associated cervical cancer and may be useful for developing new treatments.

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“…It has been demonstrated that EMP1 mediates PRD resistance induced by the interaction of leukemic cells with mesenchymal stem cells (16). EMP1 is upregulated in glioblastoma multiforme and its inhibition decreases proliferation and invasiveness of tumor (28)(29)(30). In contrast, in carcinoma of the nasopharynx, stomach, breast, urothelium, and prostate, EMP1 reduces cell migration and invasion and increases apoptosis and caspase-9 expression (27,(31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Relevance of Expression of EMP1, CASP1, and NLRP3 Genes in Pediatric B-Lineage Acute Lymphoblastic Leukemia

et al. 2021

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Glucocorticoid (GC), such as prednisolone, is an essential component of multidrug chemotherapy regimen for pediatric acute lymphoblastic leukemia (ALL). Resistance to GC in leukemia cells is associated with disease progression and poor prognosis. Despite the extensive use of GC for many years, molecular mechanisms underlying its resistance in ALL have not been fully uncovered. Recent studies have shown a potential role of EMP1, CASP1, and NLRP3 genes in prednisolone response. In this study on 148 pediatric B-ALL patients, we studied these three genes to assess their association with prednisolone response measured by day 8 blast count after 7 days of induction therapy with prednisolone. Intriguingly, ALL samples exhibited higher expression of EMP1 along with a low expression of CASP1 and NLRP3 compared to disease free normal bone marrow collected from patients with solid tumors. Among the three analyzed genes, only EMP1 was found to be overexpressed in prednisolone poor responders (p=0.015). Further, a comparison of gene expression between cytogenetic subtypes revealed higher expression of EMP1 in BCR-ABL subtype. Expression of EMP1 in multiple gene expression datasets was used for gene set enrichment analysis, which revealed TNF-α, IL-2-STAT5 signaling, inflammatory responses and hypoxia as the major positively associated pathways and E2F targets as negatively associated pathways. Interestingly, the clinical remission rate was higher in CASP1 high patients (p=0.048). In univariate survival analysis, higher EMP1 expression was associated with poor prognostic measures while higher expression of NLRP3 and CASP1 was associated with better prognostic measures in our data. Further, multivariate analysis revealed an independent association of high CASP1 and NLRP3 with a better prognosis. This study strengthens the available evidence that mRNA expression of EMP1, CASP1, and NLRP3 may serve as potential biomarkers for risk stratification of pediatric B-ALL patients.

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The Pivotal Roles of the Epithelial Membrane Protein Family in Cancer Invasiveness and Metastasis

Cited by 37 publications

References 129 publications

<p>EMP1 Promotes the Proliferation and Invasion of Ovarian Cancer Cells Through Activating the MAPK Pathway</p>

<p>EMP1 Promotes the Proliferation and Invasion of Ovarian Cancer Cells Through Activating the MAPK Pathway</p>

Markers of Angiogenesis, Lymphangiogenesis, and Epithelial–Mesenchymal Transition (Plasticity) in CIN and Early Invasive Carcinoma of the Cervix: Exploring Putative Molecular Mechanisms Involved in Early Tumor Invasion

Prognostic Relevance of Expression of EMP1, CASP1, and NLRP3 Genes in Pediatric B-Lineage Acute Lymphoblastic Leukemia

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