A Mitochondrial Switch Promotes Tumor Metastasis

PaoloE Porporato, ValéryL Payen, Jhudit Pérez-Escuredo, ChristopheJ DeSaedeleer, Pierre Danhier, Tamara Copetti, Suveera Dhup, Morgane Tardy, Thibaut Vazeille, Caroline Bouzin, Olivier Feron, Carine Michiels, Bernard Gallez, Pierre Sonveaux

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Metastatic progression of cancer is associated with poor outcome, and here we examine metabolic changes underlying this process. Although aerobic glycolysis is known to promote metastasis, we have now identified a different switch primarily affecting mitochondria. The switch involves overload of the electron transport chain (ETC) with preserved mitochondrial functions but increased mitochondrial superoxide production. It provides a metastatic advantage phenocopied by partial ETC inhibition, another situation associated with enhanced superoxide production. Both cases involved protein tyrosine kinases Src and Pyk2 as downstream effectors. Thus, two different events, ETC overload and partial ETC inhibition, promote superoxide-dependent tumor cell migration, invasion, clonogenicity, and metastasis. Consequently, specific scavenging of mitochondrial superoxide with mitoTEMPO blocked tumor cell migration and prevented spontaneous tumor metastasis in murine and human tumor models. Cancer is a leading cause of death worldwide and metastatic progression is associated with poor outcome. Porporato etal. have identified a metabolic switch that allows tumor cell mitochondria to drive successful metastatic progression. At the dissemination stage, some metastatic progenitor cells undergo a mitochondrial overload, whereas others experience a moderate respiration dysfunction. Both events promote superoxide-dependent metastasis. Consequently, mitochondria-specific superoxide scavenging inhibits metastatic dissemination, which opens a new avenue for therapeutic prevention.

langueAnglais
Pages754-766
Nombre de pages13
journalCell Reports
Volume8
Numéro3
Les DOIs
étatPublié - 2014

Empreinte digitale

Superoxides
Tumors
Switches
Neoplasm Metastasis
Mitochondria
Electron Transport
Neoplasms
Scavenging
Cells
Cell Movement
src-Family Kinases
Glycolysis
Cause of Death
Respiration
Stem Cells

Citer ceci

Porporato, P., Payen, V., Pérez-Escuredo, J., DeSaedeleer, C., Danhier, P., Copetti, T., ... Sonveaux, P. (2014). A Mitochondrial Switch Promotes Tumor Metastasis. Cell Reports, 8(3), 754-766. DOI: 10.1016/j.celrep.2014.06.043
Porporato, PaoloE ; Payen, ValéryL ; Pérez-Escuredo, Jhudit ; DeSaedeleer, ChristopheJ ; Danhier, Pierre ; Copetti, Tamara ; Dhup, Suveera ; Tardy, Morgane ; Vazeille, Thibaut ; Bouzin, Caroline ; Feron, Olivier ; Michiels, Carine ; Gallez, Bernard ; Sonveaux, Pierre. / A Mitochondrial Switch Promotes Tumor Metastasis. Dans: Cell Reports. 2014 ; Vol 8, Numéro 3. p. 754-766
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abstract = "Metastatic progression of cancer is associated with poor outcome, and here we examine metabolic changes underlying this process. Although aerobic glycolysis is known to promote metastasis, we have now identified a different switch primarily affecting mitochondria. The switch involves overload of the electron transport chain (ETC) with preserved mitochondrial functions but increased mitochondrial superoxide production. It provides a metastatic advantage phenocopied by partial ETC inhibition, another situation associated with enhanced superoxide production. Both cases involved protein tyrosine kinases Src and Pyk2 as downstream effectors. Thus, two different events, ETC overload and partial ETC inhibition, promote superoxide-dependent tumor cell migration, invasion, clonogenicity, and metastasis. Consequently, specific scavenging of mitochondrial superoxide with mitoTEMPO blocked tumor cell migration and prevented spontaneous tumor metastasis in murine and human tumor models. Cancer is a leading cause of death worldwide and metastatic progression is associated with poor outcome. Porporato etal. have identified a metabolic switch that allows tumor cell mitochondria to drive successful metastatic progression. At the dissemination stage, some metastatic progenitor cells undergo a mitochondrial overload, whereas others experience a moderate respiration dysfunction. Both events promote superoxide-dependent metastasis. Consequently, mitochondria-specific superoxide scavenging inhibits metastatic dissemination, which opens a new avenue for therapeutic prevention.",
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Porporato, P, Payen, V, Pérez-Escuredo, J, DeSaedeleer, C, Danhier, P, Copetti, T, Dhup, S, Tardy, M, Vazeille, T, Bouzin, C, Feron, O, Michiels, C, Gallez, B & Sonveaux, P 2014, 'A Mitochondrial Switch Promotes Tumor Metastasis' Cell Reports, VOL. 8, Numéro 3, p. 754-766. DOI: 10.1016/j.celrep.2014.06.043

A Mitochondrial Switch Promotes Tumor Metastasis. / Porporato, PaoloE; Payen, ValéryL; Pérez-Escuredo, Jhudit; DeSaedeleer, ChristopheJ; Danhier, Pierre; Copetti, Tamara; Dhup, Suveera; Tardy, Morgane; Vazeille, Thibaut; Bouzin, Caroline; Feron, Olivier; Michiels, Carine; Gallez, Bernard; Sonveaux, Pierre.

Dans: Cell Reports, Vol 8, Numéro 3, 2014, p. 754-766.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - A Mitochondrial Switch Promotes Tumor Metastasis

AU - Porporato,PaoloE

AU - Payen,ValéryL

AU - Pérez-Escuredo,Jhudit

AU - DeSaedeleer,ChristopheJ

AU - Danhier,Pierre

AU - Copetti,Tamara

AU - Dhup,Suveera

AU - Tardy,Morgane

AU - Vazeille,Thibaut

AU - Bouzin,Caroline

AU - Feron,Olivier

AU - Michiels,Carine

AU - Gallez,Bernard

AU - Sonveaux,Pierre

PY - 2014

Y1 - 2014

N2 - Metastatic progression of cancer is associated with poor outcome, and here we examine metabolic changes underlying this process. Although aerobic glycolysis is known to promote metastasis, we have now identified a different switch primarily affecting mitochondria. The switch involves overload of the electron transport chain (ETC) with preserved mitochondrial functions but increased mitochondrial superoxide production. It provides a metastatic advantage phenocopied by partial ETC inhibition, another situation associated with enhanced superoxide production. Both cases involved protein tyrosine kinases Src and Pyk2 as downstream effectors. Thus, two different events, ETC overload and partial ETC inhibition, promote superoxide-dependent tumor cell migration, invasion, clonogenicity, and metastasis. Consequently, specific scavenging of mitochondrial superoxide with mitoTEMPO blocked tumor cell migration and prevented spontaneous tumor metastasis in murine and human tumor models. Cancer is a leading cause of death worldwide and metastatic progression is associated with poor outcome. Porporato etal. have identified a metabolic switch that allows tumor cell mitochondria to drive successful metastatic progression. At the dissemination stage, some metastatic progenitor cells undergo a mitochondrial overload, whereas others experience a moderate respiration dysfunction. Both events promote superoxide-dependent metastasis. Consequently, mitochondria-specific superoxide scavenging inhibits metastatic dissemination, which opens a new avenue for therapeutic prevention.

AB - Metastatic progression of cancer is associated with poor outcome, and here we examine metabolic changes underlying this process. Although aerobic glycolysis is known to promote metastasis, we have now identified a different switch primarily affecting mitochondria. The switch involves overload of the electron transport chain (ETC) with preserved mitochondrial functions but increased mitochondrial superoxide production. It provides a metastatic advantage phenocopied by partial ETC inhibition, another situation associated with enhanced superoxide production. Both cases involved protein tyrosine kinases Src and Pyk2 as downstream effectors. Thus, two different events, ETC overload and partial ETC inhibition, promote superoxide-dependent tumor cell migration, invasion, clonogenicity, and metastasis. Consequently, specific scavenging of mitochondrial superoxide with mitoTEMPO blocked tumor cell migration and prevented spontaneous tumor metastasis in murine and human tumor models. Cancer is a leading cause of death worldwide and metastatic progression is associated with poor outcome. Porporato etal. have identified a metabolic switch that allows tumor cell mitochondria to drive successful metastatic progression. At the dissemination stage, some metastatic progenitor cells undergo a mitochondrial overload, whereas others experience a moderate respiration dysfunction. Both events promote superoxide-dependent metastasis. Consequently, mitochondria-specific superoxide scavenging inhibits metastatic dissemination, which opens a new avenue for therapeutic prevention.

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U2 - 10.1016/j.celrep.2014.06.043

DO - 10.1016/j.celrep.2014.06.043

M3 - Article

VL - 8

SP - 754

EP - 766

JO - Cell Reports

T2 - Cell Reports

JF - Cell Reports

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Porporato P, Payen V, Pérez-Escuredo J, DeSaedeleer C, Danhier P, Copetti T et al. A Mitochondrial Switch Promotes Tumor Metastasis. Cell Reports. 2014;8(3):754-766. Disponible �, DOI: 10.1016/j.celrep.2014.06.043