DLG1 polarity protein expression associates with the disease progress of low-grade cervical intraepithelial lesions

Cavatorta, Ana Laura; Gregorio, Alejandra Di; Valdano, Marina Paula Bugnon; Marziali, Federico; Cabral, Mariela; Bottai, Hebe; Cittadini, Jorge; Nocito, Ana Lía; Gardiol, Daniela

doi:10.1016/j.yexmp.2016.12.008

Cited by 15 publications

(18 citation statements)

References 27 publications

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“…However, striking changes in DLG1 expression were also observed in the early onset of disease, namely the preceding low-grade intraepithelial lesions (LSIL). In certain LSIL cases, reduced localization at the cell borders was evidently accompanied by increased expression in the cytoplasmic region (Cavatorta et al, 2004;Cavatorta et al, 2017). Altogether, these initial analyses served to associate loss of DLG1 expression with cervical invasive stages, supporting the hypothesis of tumor suppressor functions of DLG1.…”

Section: Epithelial Cancer Progressionmentioning

confidence: 61%

Differential expression of DLG1 as a common trait in different human diseases: an encouraging issue in molecular pathology

Marziali

Dizanzo

Cavatorta

et al. 2019

Biological Chemistry

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Human disc large (DLG1) is a scaffolding protein that through the interaction with diverse cell partners participates in the control of key cellular processes such as polarity, proliferation and migration. Experimental data have mainly identified DLG1 as a tumor suppressor. An outstanding point for DLG1 protein is that altered DLG1 expression andDLG1gene mutations were observed in different pathologies, including cancer and neurological and immunological disorders. Evident changes in DLG1 abundance and/or cell localization were identified in a number of studies suggesting its participation in molecular mechanisms responsible for the development of such illnesses. In this review, we focus on some of the latest findings regarding DLG1 alterations in different diseases as well as its potential use as a biomarker for pathological progression. We further address the current knowledge on the molecular mechanisms regulating DLG1 expression and the posttranslational modifications that may affect DLG1 cell localization and functions. Despite the advances in this field, there are still open questions about the precise molecular link between alterations in DLG1 expression and the development of each specific pathology. The complete understanding of this concern will give us new scenarios for the design of promising diagnosis and therapeutic tools.

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Section: Epithelial Cancer Progressionmentioning

confidence: 61%

Differential expression of DLG1 as a common trait in different human diseases: an encouraging issue in molecular pathology

Marziali

Dizanzo

Cavatorta

et al. 2019

Biological Chemistry

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“…In this report, we present new insights into the effect of HPV proteins over the expression of the PDZ polarity regulator DLG1. Recently, we showed that changes in the levels and cell distribution of DLG1 in HPVassociated lesions may have an important role in tumour progression [17]. Remarkably, the loss of DLG1 expression at cell to cell contact (normal localization), together with an increase in DLG1 levels and unusual cytoplasmic distribution [15,16], were also detected in biopsies derived from other tumours, like colon adenocarcinoma [16,36] and breast cancer [37,38].…”

Section: Discussionmentioning

confidence: 97%

“…As mentioned before, DLG1 deregulation has been observed in histological samples and organotypic raft cultures, which expressed not only E6 but also the HPV-E7 oncoprotein [16][17][18]. Therefore, we wanted to investigate in more detail the specific contribution of E7 to the observed changes in DLG1 expression.…”

Section: The Co-expression Of Hpv-18 E6 and E7 Proteins Promotes The mentioning

confidence: 92%

“…Interestingly, such differential expression was demonstrated to be a very efficient marker of progression of low grade SILs (LSILs) to malignancy. Indeed, LSILs showing an accumulation of DLG1 in the cytoplasm progressed to high-grade SIL (HSIL), whereas those that retained DLG1 expression at the cell borders regressed to normal epithelial [17]. The observed changes in DLG1 expression could be significant for HPV pathogenesis since DLG1 normal functions strictly rely on its correct subcellular distribution [9,10].…”

Section: Introductionmentioning

confidence: 99%

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HPV E6 and E7 oncoproteins cooperatively alter the expression of Disc Large 1 polarity protein in epithelial cells

et al. 2020

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Background: Persistent infection with high-risk Human Papillomavirus (HPVs) is associated with the development of cervical cancer. The transforming capacity of these viruses relies on the cooperative action of the E6 and E7 viral oncoproteins. Among the oncogenic activities of E6, the interaction and interference with cell polarity PDZ proteins have been well established. One of the most characterized PDZ targets of HPV E6 is human Disc large 1 (DLG1), a scaffolding protein involved in the control of cell polarity and proliferation. Interestingly, in cervical squamous intraepithelial lesions, alterations in DLG1 expression were observed in association to tumour progression. Moreover, the expression of both HPV E6 and E7 proteins may be responsible for the changes in DLG1 abundance and cell localization observed in the HPV-associated lesions. Methods: Due to the relevance of DLG1 deregulation in tumour development, we have performed an in-depth investigation of the expression of DLG1 in the presence of the HPV oncoproteins in epithelial cultured cells. The effects of HPV E6 and E7 proteins on DLG1 abundance and subcellular localization were assessed by western blot and confocal fluorescence microscopy, respectively. Results: We demonstrated that the relative abundance of HPV-18 E6 and DLG1 is a key factor that contributes to defining the expression abundance of both proteins. We also show here that a high expression level of DLG1 may negatively affect HPV-18 E6 nuclear expression. Moreover, the co-expression of HPV-18 E6 and E7 produces a striking effect on DLG1 subcellular localization and a co-distribution in the cytoplasmic region. Interestingly, HPV-18 E7 is also able to increase DLG1 levels, likely by rescuing it from the E6-mediated proteasomal degradation. Conclusions: In general, the data suggest that HPV-18 E6 and E7 may have opposing activities in regards to the regulation of DLG1 levels and may cooperatively contribute to its subcellular redistribution in the HPV context. These findings constitute a step forward in understanding the differential expression of DLG1 during tumour progression in an HPV-associated model.

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“…DLG1 (discs large MAGUK scaffold protein 1) is a scaffolding protein that, through interaction with diverse cell partners, participates in the control of key cellular processes such as polarity, proliferation, and migration [92]. Cavatorta et al [93] reported that the DLG1 gene encodes a member of the MAGUK protein family involved in the polarization of epithelial cells. In mouse, DLG1 is expressed at high levels in oocytes and granulosa cells [94].…”

Section: Candidate Gene Identificationmentioning

confidence: 99%

Genome-Wide Association Study Reveals Candidate Genes for Litter Size Traits in Pelibuey Sheep

Hernández-Montiel

Martínez-Núñez

Ramón-Ugalde

et al. 2020

Animals

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The Pelibuey sheep has adaptability to climatic variations, resistance to parasites, and good maternal ability, whereas some ewes present multiple births, which increases the litter size in farm sheep. The litter size in some wool sheep breeds is associated with the presence of mutations, mainly in the family of the transforming growth factor β (TGF-β) genes. To explore genetic mechanisms underlying the variation in litter size, we conducted a genome-wide association study in two groups of Pelibuey sheep (multiparous sheep with two lambs per birth vs. uniparous sheep with a single lamb at birth) using the OvineSNP50 BeadChip. We identified a total of 57 putative SNPs markers (p < 3.0 × 10−3, Bonferroni correction). The candidate genes that may be associated with litter size in Pelibuey sheep are CLSTN2, MTMR2, DLG1, CGA, ABCG5, TRPM6, and HTR1E. Genomic regions were also identified that contain three quantitative trait loci (QTLs) for aseasonal reproduction (ASREP), milk yield (MY), and body weight (BW). These results allowed us to identify SNPs associated with genes that could be involved in the reproductive process related to prolificacy.

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DLG1 polarity protein expression associates with the disease progress of low-grade cervical intraepithelial lesions

Cited by 15 publications

References 27 publications

Differential expression of DLG1 as a common trait in different human diseases: an encouraging issue in molecular pathology

Differential expression of DLG1 as a common trait in different human diseases: an encouraging issue in molecular pathology

HPV E6 and E7 oncoproteins cooperatively alter the expression of Disc Large 1 polarity protein in epithelial cells

Genome-Wide Association Study Reveals Candidate Genes for Litter Size Traits in Pelibuey Sheep

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