Nox1-dependent superoxide production controls colon adenocarcinoma cell migration

Sadok, Amine; Bourgarel-Rey, Véronique; Gattacceca, Florence; Penel, Claude; Lehmann, Maxime; Kovacic, Hervé

doi:10.1016/j.bbamcr.2007.10.010

Cited by 89 publications

(81 citation statements)

References 42 publications

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“…This view could be supported by our current finding. Recently, Nox1 activation by arachidonic acid through 12-lipoxygenase and protein kinase C␦ was also reported to augment migration of CaCO-2 cells (36). However, this study did not explore the involvement of RhoGTPase signaling, and its relevance to our study is unclear at present.…”

Section: Discussioncontrasting

confidence: 48%

Reactive Oxygen Generated by NADPH Oxidase 1 (Nox1) Contributes to Cell Invasion by Regulating Matrix Metalloprotease-9 Production and Cell Migration

Shirakawa

Adachi

Mitsushita

et al. 2010

Journal of Biological Chemistry

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A mediating role of the reactive oxygen species-generating enzyme Nox1 has been suggested for Ras oncogene transformation phenotypes including anchorage-independent cell growth, augmented angiogenesis, and tumorigenesis. However, little is known about whether Nox1 signaling regulates cell invasiveness. Here, we report that the cell invasion activity was augmented in K-Ras-transformed normal rat kidney cells and attenuated by transfection of Nox1 small interference RNAs (siRNAs) into the cells. Diphenyleneiodonium (DPI) or Nox1 siRNAs blocked up-regulation of matrix metalloprotease-9 at both protein and mRNA levels in K-Ras-transformed normal rat kidney cells. Furthermore, DPI and Nox1 siRNAs inhibited the activation of IKK␣ kinase and the degradation of IB␣, suppressing the NFB-dependent matrix metalloprotease-9 promoter activity. Additionally, epidermal growth factor-stimulated migration of CaCO-2 cells was abolished by DPI and Nox1 siRNAs, indicating the requirement of Nox1 activity for the motogenic effect of epidermal growth factor. This Nox1 action was mediated by down-regulation of the Rho activity through the low molecular weight protein-tyrosine phosphatase-p190RhoGAP-dependent mechanism. Taken together, our findings define a mediating role of Nox1-generated reactive oxygen species in cell invasion processes, most notably metalloprotease production and cell motile activity.

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Section: Discussioncontrasting

confidence: 48%

Reactive Oxygen Generated by NADPH Oxidase 1 (Nox1) Contributes to Cell Invasion by Regulating Matrix Metalloprotease-9 Production and Cell Migration

Shirakawa

Adachi

Mitsushita

et al. 2010

Journal of Biological Chemistry

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“…By using shRNA directed against Nox1, we confirmed that the DPI effect relies on Nox1 inhibition in our experimental model (6). We showed that the transient Nox1-dependent superoxide production affects the ␣2 integrin expression level and cell migration direction (6,38). The GTPase RhoA is a well-known regulator of actin stress fiber formation and focal adhesion assembly (13) and a downstream target for NADPH oxidase and ROS (31,41).…”

Section: Resultsmentioning

confidence: 59%

“…Control plasmid pRk5 and plasmid pRk5-RhoA V14 were kindly given by Alan Hall (Sloan-Kettering Cancer Center). Nox1 short hairpin RNA (shRNA) was previously validated and described (6,38). Transfected cells were serum depleted for 48 h, detached with 0.25% trypsin, and seeded onto Col-I-precoated plates (10 g/ml).…”

Section: Materials and Reagentsmentioning

confidence: 99%

“…Abrogation of Nox1-dependent ROS production by diphenyleneiodonium (DPI) or small interfering RNA restores RhoA activation and actin stress fiber formation (41). More recently, several groups have highlighted a key role of Nox1 in the control of growth factorinduced migration (16,38,40). Cancer cells probably undergo random migration during metastasis, but their migration can be directed by cytokine gradients and/or associated with ECM fibers (29,55).…”

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confidence: 99%

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NADPH Oxidase 1 Controls the Persistence of Directed Cell Migration by a Rho-Dependent Switch of α2/α3 Integrins

Sadok

Pierrès

Dahan

et al. 2009

Molecular and Cellular Biology

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NADPH oxidase 1 (Nox1) is expressed mainly in colon epithelial cells and produces superoxide ions as a primary function. We showed that Nox1 knockdown inhibits directional persistence of migration on collagen I. This paper dissects the mechanism by which Nox1 affects the direction of colonic epithelial cell migration in a two-dimensional model. Transient activation of Nox1 during cell spreading on collagen 1 temporarily inactivated RhoA and led to efficient exportation of ␣2␤1 integrin to the cell surface, which supported persistent directed migration. Nox1 knockdown led to a loss of directional migration which takes place through a RhoA-dependent ␣2/␣3 integrin switch. Transient RhoA overactivation upon Nox1 inhibition led to transient cytoskeletal reorganization and increased cell-matrix contact associated with a stable increase in ␣3 integrin cell surface expression. Blocking of ␣3 integrin completely reversed the loss of directional persistence of migration. In this model, Nox1 would represent a switch between random and directional migration through RhoA-dependent integrin cell surface expression modulation.The two well-recognized defining hallmarks of cancer are uncontrolled proliferation and invasion (14). The conversion of a static primary tumor into an invasive disseminating metastasis involves an enhanced migratory ability of the tumor cells. Tumor cells use migration mechanisms that are similar, if not identical, to those that occur in normal cells during physiological processes such as embryonic morphogenesis, wound healing, and immune-cell trafficking (10). To migrate, cells must acquire a spatial asymmetry that enables them to turn intracellularly generated forces into net cell body translocation. Dynamic assembly and disassembly of integrin-mediated adhesion and cytoskeletal reorganization are necessary for efficient migration (29). Integrins are heterodimeric integral membrane proteins composed of an ␣ chain and a ␤ chain. Depending on the cell type and extracellular matrix (ECM) substrate, focal contact assembly and migration can be regulated by different integrins. Collagen receptors include ␣1␤1, ␣2␤1, and ␣3␤1 integrins. ␣1␤1 and ␣3␤1 integrins also bind laminin and have less affinity for collagen than does integrin ␣2␤1 (47). The intrinsic propensity of cells to continue migrating in the same direction without turning is closely related to integrin/cytoskeletal interaction, which is known to regulate tractional forces, resulting in modulation of the speed and direction of cell migration (33). Interestingly, different integrin-ECM associations might have opposite effects on the regulation of the directionality of migration. Danen et al. have shown that adhesion to fibronectin by ␣v␤3 promotes persistent migration through activation of the actin-severing protein cofilin, which results in a polarized phenotype with a single broad lamellipod at the leading edge. In contrast, adhesion to fibronectin by ␣5␤1 instead leads to phosphorylation/inactivation of cofilin and these cells fail to polari...

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“…12-lipoxygenase (12-LOX), a member of the lipoxygenase superfamily, catalyzes the stereospecific oxygenation of AA to 12(S)-hydroperoxyeicosatetraenoic acid (HPETE) and 12(S)-hydroxyeicosatetraenoic acid (HETE) (40). At least three types of 12-LOX have been characterized--platelet-type, leukocyte-type, and epidermal 12-LOX.…”

Section: -Lox Metabolites and Rosmentioning

confidence: 99%

Cytosolic phospholipase A₂, lipoxygenase metabolites, and reactive oxygen species

Kim

Kim²,

Kim³

2008

BMB Reports

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Reactive oxygen species (ROS) are generated in mammalian cells via both enzymatic and non-enzymatic mechanisms. Although certain ROS production pathways are required for the performance of specific physiological functions, excessive ROS generation is harmful, and has been implicated in the pathogenesis of a number of diseases. Among the ROS-producing enzymes, NADPH oxidase is widely distributed among mammalian cells, and is a crucial source of ROS for physiological and pathological processes. Reactive oxygen species are also generated by arachidonic acid (AA) metabolites, which are released from membrane phospholipids via the activity of cytosolic phospholipase A2 (cPLA2). In this study, we describe recent studies concerning the generation of ROS by AA metabolites. In particular, we have focused on the manner in which AA metabolism via lipoxygenase (LOX) and LOX metabolites contributes to ROS generation. By elucidating the signaling mechanisms that link LOX and LOX metabolites to ROS, we hope to shed light on the variety of physiological and pathological mechanisms associated with LOX metabolism. [BMB reports 2008; 41(8): 555-559]Reactive oxygen species (ROS) are highly reactive O2 metabolites, such as superoxide radicals (O2 •− ), hydrogen peroxide (H2O2), and hydroxyl radicals (•OH) (1). Although ROS have classically been regarded as cytotoxic and harmful, recent evidence suggests that superoxide radicals and H2O2 may also function as essential components of signal transduction pathways (2). ROS have also been implicated in cell proliferation, survival, migration, and adhesion pathways (1-4). The targets of ROS include key signaling molecules, such as transcription factor nuclear factor κB (NF-κB), mitogen-activated protein kinases, tyrosine phosphatases, and phosphatase and tensin homologue (PTEN), which hydrolyzes the 3-phosphate group of the bioactive lipid, phosphatidylinositol 3,4,5-triphosphate (1, 5-7).Until recently, phagocytic NADPH oxidase was the bestcharacterized example of ROS production in mammalian cells. This enzyme catalyzes the respiratory burst (1) and is comprised of a catalytic subunit (i.e., gp91phox, or NOX2), regulatory subunits (i.e., p22phox, p47phox, p40phox, and p67phox), and a small GTPase (i.e., Rac). Non-phagocytic cells also generate significant quantities of ROS, albeit in much smaller amounts than in phagocytes (i.e., only a small percentage of the ROS levels detected in activated neutrophils) (2). In non-phagocytic cells, ROS are produced via a variety of cellular oxidative metabolic processes, including NADPH oxidase, xanthine oxidase, arachidonic acid (AA) metabolism by cyclooxygenases (COX; more accurately, prostaglandin G/H synthase) and lipoxygenases (LOX), and the mitochondrial respiratory chain (2). In the 1990s, an increase in the number of sensitive assays available facilitated the detection of ever-smaller quantities of ROS, as well as enzyme generation in a variety of non-phagocytic cell types. Over the past several years, non-phagocytic NADPH oxidases (e.g., NOX1,...

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Nox1-dependent superoxide production controls colon adenocarcinoma cell migration

Cited by 89 publications

References 42 publications

Reactive Oxygen Generated by NADPH Oxidase 1 (Nox1) Contributes to Cell Invasion by Regulating Matrix Metalloprotease-9 Production and Cell Migration

Reactive Oxygen Generated by NADPH Oxidase 1 (Nox1) Contributes to Cell Invasion by Regulating Matrix Metalloprotease-9 Production and Cell Migration

NADPH Oxidase 1 Controls the Persistence of Directed Cell Migration by a Rho-Dependent Switch of α2/α3 Integrins

Cytosolic phospholipase A₂, lipoxygenase metabolites, and reactive oxygen species

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Nox1-dependent superoxide production controls colon adenocarcinoma cell migration

Cited by 89 publications

References 42 publications

Reactive Oxygen Generated by NADPH Oxidase 1 (Nox1) Contributes to Cell Invasion by Regulating Matrix Metalloprotease-9 Production and Cell Migration

Reactive Oxygen Generated by NADPH Oxidase 1 (Nox1) Contributes to Cell Invasion by Regulating Matrix Metalloprotease-9 Production and Cell Migration

NADPH Oxidase 1 Controls the Persistence of Directed Cell Migration by a Rho-Dependent Switch of α2/α3 Integrins

Cytosolic phospholipase A2, lipoxygenase metabolites, and reactive oxygen species

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Cytosolic phospholipase A₂, lipoxygenase metabolites, and reactive oxygen species