Desmoglein 3 (Dsg3) expression in cancer: A tissue microarray study on 15,869 tumors

Viehweger, Florian; Azem, Ahmad; Gorbokon, Natalia; Uhlig, Ria; Lennartz, Maximilian; Rico, Sebastian Dwertmann; Kind, Simon; Reiswich, Viktor; Kluth, Martina; Hube‐Magg, Claudia; Bernreuther, Christian; Büscheck, Franziska; Clauditz, Till S.; Fraune, Christoph; Jacobsen, Frank; Krech, Till; Lebok, Patrick; Steurer, Stefan; Burandt, Eike; Minner, Sarah; Marx, Andreas; Simon, Ronald; Sauter, Guido; Menz, Anne; Hinsch, Andrea

doi:10.1016/j.prp.2022.154200

Cited by 3 publications

(2 citation statements)

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“…Myklebust [6] showed that high expression of DSG1 was associated with tumor size, lymph node metastasis and poorer prognosis in squamous cell carcinoma of the anal canal. Similarly, another study [33] showed that high DSG3 expression was associated with invasive growth in urothelium carcinoma and colorectal cancers. All of these studies demonstrated the pro-cancer function of DSG3, which is consistent with the ndings in this study which showed that DSG3 expression was elevated in PAAD patients and signi cantly associated with poor patient prognosis.…”

Section: Discussionmentioning

confidence: 79%

Clinicopathological Features, Immune Infiltration Landscape and Involved Signaling Pathways of the desmogleins family in Pancreatic Adenocarcinoma

Lin

Duan

et al. 2023

Preprint

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Background A growing body of evidence suggests that the DSG family plays a key role in tumorigenesis and progression; however, the function of DSG family members in PAAD remains unclear. Methods Comprehensive bioinformatics analysis was performed to investigate the clinicopathological characteristics, prognostic value, imnological features, and functional mechanisms of DSG family members in PAAD, using UALCAN, the HPA, Kaplan–Meier Plotter, cBioPortal, TISIDB, LinkedOmics, STRING and GSCALite Database. Results The expression of DSG family members was significantly higher in PAAD tissues compared with paraneoplastic or normal tissues, and their copy number variation was significantly associated with poorer clinicopathological characteristics and prognosis in PAAD patients. Furthermore, the roles of DSG family members in immune regulation are diverse and complex. Mechanistically, TP53 mutations are significantly associated with promoter methylation and the expression of DSG family members, and EGFR may be key to the role of DSG family members in PAAD. DSG family members activate several oncogenic pathways, including EMT, PI3K/AKT, and RAS/MAPK signaling pathway. In addition, we found that the expression of DSG family members was significantly correlated with sensitivity to multiple conventional chemotherapeutic agents and novel targeted drugs. Conclusions DSG family members play an oncogenic role in the development of PAAD and may serve as novel biomarkers or therapeutic targets.

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Section: Discussionmentioning

confidence: 79%

Clinicopathological Features, Immune Infiltration Landscape and Involved Signaling Pathways of the desmogleins family in Pancreatic Adenocarcinoma

Lin

Duan

et al. 2023

Preprint

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“…BCC tumor cells possess desmosomes, as demonstrated by electron microscopy, which has shown that the relative surface area of desmosomes on the plasma membrane is increased, 11 and by immunohistochemistry, which reveals desmosomal antigens on tumor cells 12 ; therefore, the finding of acantholysis in BCC should not really be unexpected; however, the reason why it has only exceptionally been observed in BCC is unknown. The biological impact of acantholysis in keratinocytic tumors is not well-known.…”

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confidence: 99%

Acantholytic Nodular Basal Cell Carcinoma

Kanitakis

2023

The American Journal of Dermatopathology

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Acantholysis is a microscopic finding describing the breakdown of desmosomes of keratinocytes and the formation of intraepithelial clefts after the loss of cohesion of keratinocytes. It can be observed in keratinocytic neoplasms, typically actinic keratoses and squamous cell carcinomas, and defines the acantholytic variants of these entities. Acantholysis has so far been reported in only 4 cases of basal cell carcinomas (BCCs), mainly of the superficial type. A case of an otherwise typical nodular BCC showing features of acantholysis is presented here. Because BCCs are keratinocytic neoplasms, the finding of acantholysis in them is not totally surprising; however, the reason why it is only very exceptionally observed in BCCs is unclear.

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Comparative Transcriptome Analysis Identifies Desmoglein-3 as a Potential Oncogene in Oral Cancer Cells

Wan,

Teh,

Mastroianni

et al. 2023

Cells

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The role of desmoglein-3 (DSG3) in oncogenesis is unclear. This study aimed to uncover molecular mechanisms through comparative transcriptome analysis in oral cancer cells, defining potential key genes and associated biological processes related to DSG3 expression. Four mRNA libraries of oral squamous carcinoma H413 cell lines were sequenced, and 599 candidate genes exhibited differential expression between DSG3-overexpressing and matched control lines, with 12 genes highly significantly differentially expressed, including 9 upregulated and 3 downregulated. Genes with known implications in cancer, such as MMP-13, KRT84, OLFM4, GJA1, AMOT and ADAMTS1, were strongly linked to DSG3 overexpression. Gene ontology analysis indicated that the DSG3-associated candidate gene products participate in crucial cellular processes such as junction assembly, focal adhesion, extracellular matrix formation, intermediate filament organisation and keratinocyte differentiation. Validation of RNA-Seq was performed through RT-qPCR, Western blotting and immunofluorescence analyses. Furthermore, using transmission electron microscopy, we meticulously examined desmosome morphology and revealed a slightly immature desmosome structure in DSG3-overexpressing cells compared to controls. No changes in desmosome frequency and diameter were observed between the two conditions. This study underscores intricate and multifaceted alterations associated with DSG3 in oral squamous carcinoma cells, implying a potential oncogenic role of this gene in biological processes that enable cell communication, motility and survival.

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Desmoglein 3 (Dsg3) expression in cancer: A tissue microarray study on 15,869 tumors

Cited by 3 publications

References 60 publications

Clinicopathological Features, Immune Infiltration Landscape and Involved Signaling Pathways of the desmogleins family in Pancreatic Adenocarcinoma

Clinicopathological Features, Immune Infiltration Landscape and Involved Signaling Pathways of the desmogleins family in Pancreatic Adenocarcinoma

Acantholytic Nodular Basal Cell Carcinoma

Comparative Transcriptome Analysis Identifies Desmoglein-3 as a Potential Oncogene in Oral Cancer Cells

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