ArticlePloS one2012
Dysregulation of cell polarity proteins synergize with oncogenes or the microenvironment to induce invasive behavior in epithelial cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Review
- Review
- C. elegans Afadin is required for epidermal morphogenesis and functionally interfaces with the cadherin-catenin complex and RhoGAP PAC-1/ARHGAP21.Developmental biology · 2024Article
- Afadin couples RAS GTPases to the polarity rheostat Scribble.Nature communications · 2022Article
- ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development.Frontiers in cell and developmental biology · 2022Article
- Proximity proteomics identifies PAK4 as a component of Afadin-Nectin junctions.Nature communications · 2021Article
- The molecular basis of mammary gland development and epithelial differentiation.Seminars in cell & developmental biology · 2021Review
- Cytoskeletal Organization and Cell Polarity in the Pathogenesis of Crohn's Disease.Clinical reviews in allergy & immunology · 2021Review
- Regulation of Epithelial-to-Mesenchymal Transition by Alternative Translation Initiation Mechanisms and Its Implications for Cancer Metastasis.International journal of molecular sciences · 2020Review
- The role of polarisation of circulating tumour cells in cancer metastasis.Cellular and molecular life sciences : CMLS · 2019Review
- EMT and stemness: flexible processes tuned by alternative splicing in development and cancer progression.Molecular cancer · 2017Review
- Expression of Par3 polarity protein correlates with poor prognosis in ovarian cancer.BMC cancer · 2016Article
- Par6G suppresses cell proliferation and is targeted by loss-of-function mutations in multiple cancers.Oncogene · 2016Article
- The polarity protein Scrib mediates epidermal development and exerts a tumor suppressive function during skin carcinogenesis.Molecular cancer · 2015Article
- Rewiring cell polarity signaling in cancer.Oncogene · 2015Review
- Expression of polarity genes in human cancer.Cancer informatics · 2015Article
- The Cdc42 Effector Kinase PAK4 Localizes to Cell-Cell Junctions and Contributes to Establishing Cell Polarity.PloS one · 2015Article
- Scrib heterozygosity predisposes to lung cancer and cooperates with KRas hyperactivation to accelerate lung cancer progression in vivo.Oncogene · 2014Article
- Exome sequencing identifies DLG1 as a novel gene for potential susceptibility to Crohn's disease in a Chinese family study.PloS one · 2014Article
- Emerging role of cell polarity proteins in breast cancer progression and metastasis.Breast cancer (Dove Medical Press) · 2014Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Changes in expression and localization of proteins that regulate cell and tissue polarity are frequently observed in carcinoma. However, the mechanisms by which changes in cell polarity proteins regulate carcinoma progression are not well understood. Here, we report that loss of polarity protein expression in epithelial cells primes them for cooperation with oncogenes or changes in tissue microenvironment to promote invasive behavior. Activation of ErbB2 in cells lacking the polarity regulators Scribble, Dlg1 or AF-6, induced invasive properties. This cooperation required the ability of ErbB2 to regulate the Par6/aPKC polarity complex. Inhibition of the ErbB2-Par6 pathway was sufficient to block ErbB2-induced invasion suggesting that two polarity hits may be needed for ErbB2 to promote invasion. Interestingly, in the absence of ErbB2 activation, either a combined loss of two polarity proteins, or exposure of cells lacking one polarity protein to cytokines IL-6 or TNFα induced invasive behavior in epithelial cells. We observed the invasive behavior only when cells were plated on a stiff matrix (Matrigel/Collagen-1) and not when plated on a soft matrix (Matrigel alone). Cells lacking two polarity proteins upregulated expression of EGFR and activated Akt. Inhibition of Akt activity blocked the invasive behavior identifying a mechanism by which loss of polarity promotes invasion of epithelial cells. Thus, we demonstrate that loss of polarity proteins confers phenotypic plasticity to epithelial cells such that they display normal behavior under normal culture conditions but display aggressive behavior in response to activation of oncogenes or exposure to cytokines.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.