Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA362232 | ENA |
REPOSITORIES: ENA
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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
Project description:Aim: mRNA profile of larval wing imaginal discs of Drosophila melanogaster to study the cooperation between Notch activation and loss of epithelial polarity (scrib mutation) during neoplastic growth. Results: The combination of Notch activation and scribble mutation (NS) results in mRNA expression changes that, while partly overlapping with Notch only (N), and with scrib mutation only (S), are unique to the combination
2021-10-07 | GSE185339 | GEO
Project description:Aim: Su(H) chromatin occupancy profiling by ChIP on larval wing imaginal discs of Drosophila melanogaster to study the cooperation between Notch activation and loss of epithelial polarity (scrib mutation) during neoplastic growth. Results: The combination of Notch activation and scribble mutation (NS) does not lead to a general redeployment of Su(H) binding as compared to individual conditions (Notch only (N), and scrib mutation only (S))
2021-10-08 | GSE185490 | GEO
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
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
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
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
Project description:It has long been proposed that cell competition functions to remove precancerous clones. A classical model is the removal of polarity-deficient clones such as the scribble (scrib) mutant clones in Drosophila imaginal discs. The activation of Ras, Yki or Notch signaling robustly reverses the scrib mutant clonal fate from elimination to tumorous growth. Using single-cell transcriptomics techniques to profile wing imaginal discs harboring the scrib mutant clones in combination with different signals, we found that a critical converging point downstream of Ras, Yki and Notch signals is the upregulation of Upd2, which is necessary to promote tumorous growth. Unexpectedly, while Upd2 is not required for cell survival per se, Upd2-deficient clones are efficiently wiped out from epithelia, indicating that Upd2 is a previously unrecognized cell competition factor.
2024-06-01 | GSE229909 | GEO
Project description:To identify the molecular pathway regulated by Scribble (SCRIB) in primary hunan endometrial stromal cells (ESCs) decidualization, high-throughput RNA-seq was performed to analyze the transcriptome profile in si-Ctrl or si-SCRIB transfected decidualized ESCs (dESCs).
2021-12-31 | GSE164331 | GEO
Project description:Epithelial structure and function are governed by evolutionarily conserved signaling programs. The Drosophila Activating transcription factor 3 (Atf3) prevents epithelial cell replacement during abdominal morphogenesis, yet its transcriptional targets are unknown. Here we demonstrate that Atf3 positively and negatively regulates target genes central to cytoskeleton dynamics and adhesion. Epithelial clones overexpressing Atf3 are enriched for basolateral proteins at the expense of apical identity. Strikingly, Atf3 functions downstream of the Scrib polarity module. Depleting either scrib or dlg1 induces atf3 expression, while loss of atf3 suppresses differentiation and polarity defects in cells deficient for the Scrib complex
2018-02-20 | GSE71206 | GEO