Mucin 13: Structure, Function, and Potential Roles in Cancer Pathogenesis

Maher, Diane M.; Gupta, Brij K.; Nagata, Satoshi; Jaggi, Meena; Chauhan, Subhash C.

doi:10.1158/1541-7786.mcr-10-0443

Cited by 72 publications

(63 citation statements)

References 34 publications

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“…MUC13 has a role in protection of epithelial cells from pathogen infection and also functions in cell signaling. 23 Correlated expression levels among genes in a disease-and compartment-specific manner have been used to identify functional relationships, including physical interactions and regulatory mechanisms. 24 For the HR and LR genotypes separately and independent of histologic diagnosis, we found a single coexpression module of genes that included the expression of APOL1 in TI.…”

Section: Discussionmentioning

confidence: 99%

Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE Subjects

Sampson

Robertson

Martini³

et al. 2016

Journal of the American Society of Nephrology

114

110

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APOL1 variants have been associated with renal phenotypes in blacks. To refine clinical outcomes and discover mechanisms of APOL1-associated kidney injury, we analyzed clinical and genomic datasets derived from 90 black subjects in the Nephrotic Syndrome Study Network (NEPTUNE), stratified by APOL1 risk genotype. Ninety subjects with proteinuria $0.5 g/d were enrolled at first biopsy for primary nephrotic syndrome and followed. Clinical outcomes were determined, and renal histomorphometry and sequencing of Mendelian nephrotic syndrome genes were performed. APOL1 variants were genotyped, and glomerular and tubulointerstitial transcriptomes from protocol renal biopsy cores were analyzed for differential and correlative gene expression. Analyses were performed under the recessive model (high-risk genotype defined by two risk alleles). APOL1 high-risk genotype was significantly associated with a 17 ml/min per 1.73 m 2 lower eGFR and a 69% reduction in the probability of complete remission at any time, independent of histologic diagnosis. Neither APOL1 risk group was enriched for Mendelian mutations. On renal biopsy, high-risk genotype was associated with increased fractional interstitial area, interstitial fibrosis, and tubular atrophy. Risk genotype was not associated with intrarenal APOL1 mRNA expression levels. Differential expression analysis demonstrated an increased steady-state level of five genes associated with the high-risk genotype (CXCL9, CXCL11, and UBD in glomerulus; SNOR14B and MUC13 in tubulointerstitium). APOL1 tubulointerstitial coexpression analysis showed coexpression of APOL1 mRNA levels with a group of intrarenal transcripts that together were associated with increased interstitial fibrosis and tubular atrophy. These data indicate the high-risk APOL1 genotype confers renal risk across histopathologic diagnoses.

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Section: Discussionmentioning

confidence: 99%

Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE Subjects

Sampson

Robertson

Martini³

et al. 2016

Journal of the American Society of Nephrology

114

110

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“…Interestingly, a significant number of cell juncture/adhesion proteins were biotinylated, including mucin 13; integrins β1, β5, and α6, CD44, catenin δ, desmoglein, the coxsackie virus and adenovirus receptor, and the 4F2 cell-surface antigen heavy chain ( Table I). All of these have been identified as potential cancer biomarkers (79)(80)(81)(82)(83)92), but their specific interactions with K-Ras and contributions to the progression of pancreatic cancers have yet to be thoroughly elucidated. We anticipate that analysis of these and other K-Ras interactions in pancreatic cancer cells, and in other cancers will be worthy of further scrutiny.…”

Section: Discussionmentioning

confidence: 99%

Analysis of K-Ras Interactions by Biotin Ligase Tagging

Ritchie

Mack

Harper

et al. 2017

CGP

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“…Although there are at least five cell-surface mucins expressed in the gastrointestinal tract (48), only mucin 13 (MUC13) was observed in this study, uniquely expressed in the apical EpCAM-Exos (Table I). MUC13 has been shown via immunohistochemistry to be expressed exclusively on the apical membrane surface of normal columnar and goblet cells in the gastrointestinal tract, deep in crypts; it is aberrantly expressed in a variety of epithelial carcinomas, including gastric, colorectal, and ovarian cancers, where, in addition to apical surfaces, it also localizes to lateral and basolateral surfaces (49). There was no evidence of MUC13 expression in the A33-Exos preparation.…”

Section: Fig 2 Morphological Characterization and Proteome Analysismentioning

confidence: 92%

Two Distinct Populations of Exosomes Are Released from LIM1863 Colon Carcinoma Cell-derived Organoids

Tauro

Greening

Mathias

et al. 2013

Molecular & Cellular Proteomics

364

361

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Exosomes are naturally occurring biological nanomembranous vesicles (ϳ40 to 100 nm) of endocytic origin that are released from diverse cell types into the extracellular space. They have pleiotropic functions such as antigen presentation and intercellular transfer of protein cargo, mRNA, microRNA, lipids, and oncogenic potential. Here we describe the isolation, via sequential immunocapture using anti-A33-and anti-EpCAM-coupled magnetic beads, of two distinct populations of exosomes released from organoids derived from human colon carcinoma cell line LIM1863. The exosome populations (A33-Exos and EpCAM-Exos) could not be distinguished via electron microscopy and contained stereotypical exosome markers such as TSG101, Alix, and HSP70. The salient finding of this study, revealed via gel-based LC-MS/MS, was the exclusive identification in EpCAM-Exos of the classical apical trafficking molecules CD63 (LAMP3), mucin 13 and the apical intestinal enzyme sucrase isomaltase and increased expression of dipeptidyl peptidase IV and the apically restricted pentaspan membrane glycoprotein prominin 1. In contrast, the A33-Exos preparation was enriched with basolateral trafficking molecules such as early endosome antigen 1, the Golgi membrane protein ADP-ribosylation factor, and clathrin. Our observations are consistent with EpCAM-and A33-Exos being released from the apical and basolateral surfaces, respectively, and the EpCAM-Exos proteome profile with widely published stereotypical exosomes. A proteome analysis of LIM1863-derived shed microvesicles (sMVs) was also performed in order to clearly distinguish A33-and EpCAMExos from sMVs. Intriguingly, several members of the MHC class I family of antigen presentation molecules were exclusively observed in A33-Exos, whereas neither MHC class I nor MHC class II molecules were observed via MS in EpCAM-Exos. Additionally, we report for the first time in any extracellular vesicle study the colocalization of EpCAM, claudin-7, and CD44 in EpCAM-Exos. Given that The microenvironment in which a tumor originates plays a critical role in its initiation, progression, and metastasis (1-3). Recent advances have indicated that although the microenvironment provides crucial signaling to maintain tissue architecture, inhibit cell growth, and constrain the malignant phenotype, it can also promote and induce cancer (4). In addition to cancer cells, the tumor microenvironment comprises normal cells, blood cells, secreted proteins and peptides, and constituents of the extracellular matrix that actively influence cell behavior. Secreted proteins, peptides, and physiological small molecules such as soluble cytokines and chemokines are currently recognized as the main exocrine and juxtacrine factors underlying cell-to-cell communication within the tumor microenvironment and providing the metastatic niche in distant organs (5). In addition to soluble secreted proteins and peptides, most cell types also release extracellular membrane vesicles (eMVs) 1 that transfer information between cells in the microenv...

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Mucin 13: Structure, Function, and Potential Roles in Cancer Pathogenesis

Cited by 72 publications

References 34 publications

Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE Subjects

Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE Subjects

Analysis of K-Ras Interactions by Biotin Ligase Tagging

Two Distinct Populations of Exosomes Are Released from LIM1863 Colon Carcinoma Cell-derived Organoids

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