Necrosis induction in glioblastoma cells reveals a new "bioswitch" function for the MT1-MMP/G6PT signaling axis in proMMP-2 activation versus cell death decision.

Cytoskeleton disorganization is an early step in the activation process of matrix metalloproteinase 2 (MMP-2) by membrane type 1 MMP (MT1-MMP) but is also associated with endoplasmic reticulum (ER) dysfunction and subsequent cell death. Given evidence that the ER-embedded glucose-6-phosphate transporter (G6PT) regulates glioblastoma cell survival and that MT1-MMP is a key enzyme in the cancer cell invasive phenotype, we explored the molecular link between G6PT and MT1-MMP. Cytoskeleton-disrupting agents such as concanavalin A (ConA) and cytochalasin D triggered proMMP-2 activation and cell death in U87 glioma cells. ConA decreased G6PT gene expression, an event that was also observed in cells overexpressing the full-length recombinant MT1-MMP protein. Overexpression of a membrane-bound catalytically active but cytoplasmic domain-deleted MT1-MMP was unable to downregulate G6PT gene expression or to trigger necrosis. Gene silencing of MT1-MMP with small interfering RNA prevented proMMP-2 activation and induced G6PT gene expression. ConA inhibited Akt phosphorylation, whereas overexpression of recombinant G6PT rescued the cells from ConA-induced proMMP-2 activation and increased Akt phosphorylation. Altogether, new functions of MT1-MMP in cell death signaling may be linked to those of G6PT. Our study indicates a molecular signaling axis regulating the invasive phenotype of brain tumor cells and highlights a new "bioswitch" function for G6PT in cell survival.

• Publication year

  2007

• Venue

  Neoplasia

• Publication date

  2007-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1593/NEO.07142PMID 17460777PMCID PMC1854846
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase-beta.

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  2007influential reference
• Hypoxia and Serum Deprivation‐Induced Apoptosis in Mesenchymal Stem Cells

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• Expression and localization of MT1-MMP and furin in the glomerular wall of short- and long-term diabetic rats.

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• beta-Amyloid and endoplasmic reticulum stress responses in primary neurons: effects of drugs that interact with the cytoskeleton.

  2006cited by this paper
• Morphogenesis of the Endoplasmic Reticulum: Beyond Active Membrane Expansion

  2006cited by this paper
• ER stress, hypoxia tolerance and tumor progression.

  2006cited by this paper
• The chemopreventive properties of chlorogenic acid reveal a potential new role for the microsomal glucose-6-phosphate translocase in brain tumor progression

  2006influential reference
• Endoplasmic reticulum stress signaling in disease.

  2006cited by this paper
• Mediators of endoplasmic reticulum stress‐induced apoptosis

  2006cited by this paper
• Pentose phosphate cycle oxidative and nonoxidative balance: A new vulnerable target for overcoming drug resistance in cancer

  2006cited by this paper
• Silencing of the human microsomal glucose‐6‐phosphate translocase induces glioma cell death: Potential new anticancer target for curcumin

  2006influential reference
• Ultraviolet radiation (UV) induces reorganization of actin cytoskeleton in CHOAA8 cells.

  2006cited by this paper
• Targeting endoplasmic reticulum protein transport: a novel strategy to kill malignant B cells and overcome fludarabine resistance in CLL.

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• Endoplasmic reticulum: A metabolic compartment

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• Wnt Signaling Regulates the Invasion Capacity of Human Mesenchymal Stem Cells

  2006cited by this paper
• Cell Death Independent of Caspases: A Review

  2005cited by this paper
• Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis.

  2005cited by this paper
• The transmembrane domain is essential for the microtubular trafficking of membrane type-1 matrix metalloproteinase (MT1-MMP)

  2005influential reference
• Targeting the phosphatidylinositol-3 kinase/Akt pathway for the treatment of cancer.

  2005cited by this paper
• Roles of membrane‐type matrix metalloproteinase‐1 in tumor invasion and metastasis

  2005cited by this paper
• Molecular neuro-oncology and the development of targeted therapeutic strategies for brain tumors Part 5: apoptosis and cell cycle

  2005cited by this paper
• Disruption of actin cytoskeleton and anchorage-dependent cell spreading induces apoptotic death of mouse neural crest cells cultured in vitro.

  2005cited by this paper
• Palmitoylation at Cys574 is essential for MT1‐MMP to promote cell migration

  2005cited by this paper
• Possible future issues in the treatment of glioblastomas: special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis.

  2005cited by this paper
• mTOR promotes survival and astrocytic characteristics induced by Pten/AKT signaling in glioblastoma.

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• Lysosomes and endoplasmic reticulum: targets for improved, selective anticancer therapy.

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• Membrane type 1-matrix metalloproteinase induces endothelial cell morphogenic differentiation by a caspase-dependent mechanism.

  2005cited by this paper
• Membrane type 1-matrix metalloproteinase promotes human prostate cancer invasion and metastasis

  2005influential reference
• The prognostic significance of phosphatidylinositol 3-kinase pathway activation in human gliomas.

  2004cited by this paper
• Src-mediated Tyrosine Phosphorylation of Caveolin-1 Induces Its Association with Membrane Type 1 Matrix Metalloproteinase*

  2004cited by this paper
• Bio-switches: what makes them robust?

  2004cited by this paper
• Pathways of apoptotic and non-apoptotic death in tumour cells

  2004cited by this paper
• Genetic Alterations and Aberrant Expression of Genes Related to the Phosphatidyl‐lnositol‐3′‐Kinase/Protein Kinase B (Akt) Signal Transduction Pathway in Glioblastomas

  2003cited by this paper
• Synergistic augmentation of antimicrotubule agent-induced cytotoxicity by a phosphoinositide 3-kinase inhibitor in human malignant glioma cells.

  2003cited by this paper
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  2003cited by this paper
• Inhibition of microsomal glucose-6-phosphate transport in human neutrophils results in apoptosis: a potential explanation for neutrophil dysfunction in glycogen storage disease type 1b.

  2003cited by this paper
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  2003cited by this paper
• Migrating glioma cells activate the PI3-K pathway and display decreased susceptibility to apoptosis

  2003cited by this paper
• Metabolic profiling of cell growth and death in cancer: applications in drug discovery.

  2002cited by this paper
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  2002cited by this paper
• Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials.

  2002cited by this paper
• Necrosis and Glioblastoma: A Friend or a Foe? A Review and a Hypothesis

  2002cited by this paper
• Hypoxia and VEGF mRNA expression in human tumors.

  2001cited by this paper
• The glucose-regulated proteins: stress induction and clinical applications.

  2001cited by this paper
• Death-associated protein 3 (Dap-3) is overexpressed in invasive glioblastoma cells in vivo and in glioma cell lines with induced motility phenotype in vitro.

  2001cited by this paper
• Rapid activation of matrix metalloproteinase-2 by glioma cells occurs through a posttranslational MT1-MMP-dependent mechanism.

  2000cited by this paper
• Effects of glucose on matrix metalloproteinase and plasmin activities in mesangial cells: possible role in diabetic nephropathy.

  2000cited by this paper
• New lessons in the regulation of glucose metabolism taught by the glucose 6-phosphatase system.

  2000cited by this paper
• Inactivation of the Glucose 6-Phosphate Transporter Causes Glycogen Storage Disease Type 1b*

  1999cited by this paper
• Matrix metalloproteinases and their biological function in human gliomas

  1999cited by this paper
• "...those left behind." Biology and oncology of invasive glioma cells.

  1999cited by this paper
• Glucose-6-phosphate and Ca2+ sequestration are mutually enhanced in microsomes from liver, brain, and heart.

  1998cited by this paper
• Activation of procollagenase IV by cytochalasin D and concanavalin A in cultured rat mesangial cells: linkage to cytoskeletal reorganization.

  1994cited by this paper
• The modification and assembly of proteins in the endoplasmic reticulum.

  1993cited by this paper

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  2016cites this paper
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  2016cites this paper
• Molecular Functions of Glycoconjugates in Autophagy.

  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2014cites this paper
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• matrix metalloproteinase intracellular signalling in glioblastoma cells

  2012cites this paper
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• Natural product inhibitors of glucose-6-phosphate translocase

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• Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion

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• RNA Interference-Based Therapies Against Brain Tumors: Potential Clinical Strategies

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• Maintenance of luminal NADPH in the endoplasmic reticulum promotes the survival of human neutrophil granulocytes

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• Diagnostic and prognostic role of matrix metalloproteases in cancer.

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• Neoplasia: the second decade.

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