Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Apicobasal surfaceome architecture encodes for polarized epi-thelial functionality and depends on tumor suppressor PTEN

ABSTRACT: The loss of apicobasal polarity during the epithelial-to-mesenchymal transition (EMT) is a hall-mark of cancer and metastasis. The key feature of this polarity in epithelial cells is the subdivision of the plasma membrane into apical and basolateral domains, with each orchestrating specific in-tra- and extracellular functions. Epithelial transport and signaling capacities are thought to be determined largely by the quality, quantity and nanoscale organization of proteins residing in these membrane domains, the apicobasal surfaceomes. Despite its implications for cancer, drug uptake and infection, our current knowledge of how the polarized surfaceome is organized and maintained is limited. Here we used chemoproteomic surfaceome scanning to establish proteo-type maps of apicobasal surfaceomes and reveal quantitative distributions of i.a. surface proteas-es, phosphatases and tetraspanins as potential key regulators of polarized cell functionality. We show further that tumor-suppressor PTEN regulates polarized surfaceome architecture and un-cover a potential role in collective cell migration. Our differential surfaceome analysis provides a molecular framework to elucidate polarized protein networks regulating epithelial functions and PTEN-associated cancer progression.

INSTRUMENT(S): Orbitrap Fusion ETD, Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Bernd Wollscheid

PROVIDER: MSV000090530 | MassIVE | Thu Oct 13 09:34:00 BST 2022

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Similar Datasets

Identification of genes responsive to change in apical polarity in the breast epithelium

Project description:Differentiation of monolayered epithelia is characterized by the formation of a basoapical polarity axis, except during the early stages of cancer development. Using mammary glandular structures (acini) produced in a three-dimensional cell culture system we have demonstrated that, in order for mammary epithelial cells to exit quiescence and enter the cell cycle, acini have to lose apical polarity. In order to identify the genes dependent on apical polarity that could control cell quiescence, and possibly other aspects of tissue homeostasis, we have used Affymetrix technology microarray analysis of the 22,277 features/genes of the Human Genome U133A 2.0 array Chip in apically polarized and non-polarized breast epithelial acinar cells in three-dimensional culture. Genes commonly down-regulated in two treatments that altered apical polarity compared to control were considered to be dependent on apical polarity status for their transcription. Apically polarized (Control) and two different populations of non-polarized human mammary epithelial cells (18-alpha-glycyrrhetinic acid =AGA, and 5-aza-2'-deoxycytidine =Aza) were used for microarray analysis containing four biological replicates (1-4) for each treatment. The two treatments that cause loss of apical polarity were compared to reference apically polarized control samples using two different statistical analysis methods (FDR and HolmM-bM-^@M-^Ys).

2012-02-29 | E-GEOD-35165 | biostudies-arrayexpress

The tumor suppressor SCRIB is a negative modulator of the Wnt/-catenin signaling (part 2)

Project description:Epithelial tissues are highly organized structures that rely on cell polarity pathways driven by membrane receptors and scaffolding proteins. SCRIBBLE is a cytoplasmic scaffold present at cell-cell junctions in polarized cells that contains LRR and PDZ domains. The current interactome of SCRIB and LRRC1 consists of 67 and 30 protein interaction partners respectively with only 9 (10%) common partners (BioGRID, version 3.5). Our study identified a protein complex associated to SCRIB stabilized by the inhibition of the proteasome and further characterize SCRIB act as negative modulator of the Wnt/β-catenin signaling.

2019-09-25 | PXD013636 | Pride

Identification of genes responsive to change in apical polarity in the breast epithelium

2012-02-29 | GSE35165 | GEO

Expression profiling of 3D 2D MDCKII epithelial morphogenesis

Project description:Formation of epithelial tissues requires the generation of apical-basal polarity and the co-ordination of this polarity between neighboring cells to form a central lumen. MDCK cell line has proven to be a powerful model to study mammalian polarized epithelia in vitro. MDCK cells plated in extracellular matrix (ECM) form cysts, a spherical structure of polarized cells enclosing a central lumen which resembles epithelial tubular structures. The morphogenetic process requires drastic changes in cell architecture, which are regulated by change in gene expression. We used microarrays to identify genes up-regulated in lumen formation. The identification of up-regulated genes could lead us to characterize novel pathways needed for this process. MDCKII cells were plated in two different conditions: Cells cultured in confluence in plastic dishes, forming polarized monolayers (2D); or cells cultured in plastic dishes covered with Matrigel (ECM) forming three dimensional cysts (3D). Comparison of both transcriptomic profiles would lead us to identify up-regulated genes in the 3D condition, which would be good candidates to be key regulators of novel processes involved in lumen morphogenesis.

2011-09-30 | E-GEOD-32495 | biostudies-arrayexpress

Effect of conditional knockout of Prkci (atypical PKC iota/lambda coding gene) in mouse enterocytes reveals robust innate immunity transcriptomic response

Project description:Atypical PKCiota/lambda is a key effector of the PAR polarity complex which is considered a master determinant of apico-basal polarity in single-layered epithelial cells. In polarized epithelial cells aPKC is exquisitely localized by the PAR6 partner to a belt nearby the tight junctions. Surprisingly, tissue specific knock out of the transgenic floxed version with villin-CRE showed a chronic inflammation phenotype. The observations were made in three different independent transgenic mouse lines and published by three different groups including ours (PMID: 27226486; PMID: 30552022; PMID: 21744423 ), which is reassuring for reproducibility. An additional double KO in both aPKC isoforms further confirmed the results (PMID: 30552022 ). The animals were viable and there was not strong diarrheal or constipation phenotype characteristic of polarity defects in intestinal epithelia. With few exceptions such as ezrin localization, apical polarity markers were generally well polarized. There were changes in cytokine expression by epithelial cells and infiltration of CD8+ T cells (PMID: 27226486; PMID: 30552022). The goal of the study was to get an unbiased catalog of the transcriptional changes induced by aPKC iota/lambda defect in intestinal epithelial cells to understand the ontology of gene expression downstream of the PAR polarity complex. The results are consistent with broad changes in NF-kB and IFN dependent transcriptional pathways, possibly mediated by ROCK and Med17 downstream of aPKCiota/lambda (PMID: 2722648; PMID: 33596087). This study was published in PMID: 33596087.

2023-06-15 | GSE235056 | GEO

The tumor suppressor SCRIB is a negative modulator of the Wnt/-catenin signaling (part 1)

Project description:Epithelial tissues are highly organized structures that rely on cell polarity pathways driven by membrane receptors and scaffolding proteins. SCRIBBLE is a cytoplasmic scaffold present at cell-cell junctions in polarized cells that contains LRR and PDZ domains as its paralogue LANO, a member of the LAP protein family. The family is composed of DENSIN-180, ERBIN, SCRIB and LRRC1. Based on phylogenic tree, LAP proteins can be split in two branches with the first branch is made up with SCRIB and LRCC1 and the second one of ERBIN and DENSIN-180. The current interactome of SCRIB and LRRC1 consists of 67 and 30 protein interaction partners respectively with only 9 (10%) common partners (BioGRID, version 3.5). Our study uncovers the proteome associated to SCRIB and LRRC1 and described for the first time protein associated to each paralogue.

2019-09-25 | PXD013647 | Pride

Mislocalization of the cell polarity protein Scribble (Scrib) induces SPARC secretion in hepatocellular carcinoma

Project description:Cell polarity is crucial for the maintenance of epithelial cell function and its loss may have an im-portant role in the development and progression of cancer. We here show that overexpression and cytoplasmic enrichment of the baso-lateral polarity complex protein Scribble (Scrib) correlates with poor prognosis of hepatocellular cancer (HCC) patients. Expression of the cytoplasmic ScribP305L in hepatocellular cells induces epithelial to mesenchymal transition (EMT) and supports HCC cell invasion in comparison to cells expressing membrane-localized ScribWT. ScribP305L induces AKT signalling through destabilization of the phosphatases phosphatase and tensin homolog (PTEN) and PH domain and leucine rich repeat protein phosphatase 1 (PHLPP1). Moreover, cytoplasmic ScribP305L stimulates the expression of secreted protein acidic and cysteine rich (SPARC) de-pending on the AP1 constituents ATF2 and JunB, which drives HCC cell invasiveness. In vivo, combined hydrodynamic delivery of ScribP305L but not ScribWT and c-MYC initiates tumour for-mation in hepatocytes and cytoplasmic Scrib correlates with AKT phosphorylation, and AP1 ex-pression in human HCC tissues. Together, overexpression and mislocalization of Scrib represents an early event involved in the initiation and progression of liver cancer.

2017-11-30 | GSE93742 | GEO

Transcriptional response to Activating transcription factor 3 (Atf3) activity in the Drosophila eye antenna imaginal disc (EAD) epithelium.

Project description:Here we describe the transcriptional response to Atf3 expression in the EAD. Atf3 is a cell polarity response gene acting downstream of the membrane-associated Scribble polarity complex. Loss of the neoplastic tumor suppressors Scribble or Dlg1 induces Atf3 expression via aPKC signaling. Using ChIP-seq we have determined that Atf3 targets are enriched for roles in cytoarchitecture. Gain of Atf3 function interferes with organization of the microtubule network, thereby disturbing vesicular trafficking processes including endocytosis, and consequently alters the distribution of key polarity proteins along the apicobasal axis. Conversely, removal of Atf3 from cells lacking Dlg1 suppresses trafficking defects and restores both the normal localization of polarity determinants and epithelial differentiation. These results thus establish loss of polarity as a novel cue that induces Atf3 and demonstrate that gain of Atf3 function drives specific hallmarks of epithelial cells deficient for the Scribble polarity module.

2018-02-20 | GSE89845 | GEO

Expression profiling of 3D 2D MDCKII epithelial morphogenesis

2011-10-01 | GSE32495 | GEO

Lgl2 executes its function as a tumor suppressor by regulating ErbB signaling in the zebrafish epidermis

Project description:Changes in tissue homeostasis, acquisition of invasive cell characteristics and tumor formation can often be linked to the loss of epithelial cell polarity. In carcinogenesis, the grade of neoplasia correlates with impaired cell polarity. In Drosophila, lgl, dlg and scribble, which are components of the epithelial apico-basal cell polarity machinery, act as tumor suppressors and orthologs of this evolutionary conserved pathway are lost in human carcinoma with high frequency. However, a mechanistic link between neoplasia and vertebrate orthologs of these tumor suppressor genes remains to be fully explored at the organismal level. Here, we show that the pen/lgl2 mutant phenotype shares two key cellular and molecular features of mammalian malignancy: cell autonomous epidermal neoplasia and epithelial-to-mesenchymal-transition (EMT) of basal epidermal cells including the differential expression of several regulators of EMT. Further we found that epidermal neoplasia and EMT in pen/lgl2 mutant epidermal cells is promoted by ErbB signalling, a pathway of high significance in human carcinomas. Intriguingly, EMT in the pen/lgl2 mutant is facilitated specifically by ErbB2 mediated E-cadherin mislocalization and not via canonical snail dependent down-regulation of E-cadherin expression. Our data reveal that pen/lgl2 functions as a tumor suppressor gene in vertebrates, establishing zebrafish pen/lgl2 mutants as a valuable cancer model.

2009-11-01 | E-MEXP-2415 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data