AMPK promotes survival of c-Myc-positive melanoma cells by suppressing oxidative stress

Research output: Contribution to journal › Journal article › Research › peer-review

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AMPK promotes survival of c-Myc-positive melanoma cells by suppressing oxidative stress. / Kfoury, Alain; Armaro, Marzia; Collodet, Caterina; Sordet-Dessimoz, Jessica; Giner, Maria Pilar; Christen, Stefan; Moco, Sofia; Leleu, Marion; de Leval, Laurence; Koch, Ute; Trumpp, Andreas; Sakamoto, Kei; Beermann, Friedrich; Radtke, Freddy.

In: EMBO Journal, Vol. 37, No. 5, e97673, 01.03.2018.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kfoury, A, Armaro, M, Collodet, C, Sordet-Dessimoz, J, Giner, MP, Christen, S, Moco, S, Leleu, M, de Leval, L, Koch, U, Trumpp, A, Sakamoto, K, Beermann, F & Radtke, F 2018, 'AMPK promotes survival of c-Myc-positive melanoma cells by suppressing oxidative stress', EMBO Journal, vol. 37, no. 5, e97673. https://doi.org/10.15252/embj.201797673

APA

Kfoury, A., Armaro, M., Collodet, C., Sordet-Dessimoz, J., Giner, M. P., Christen, S., Moco, S., Leleu, M., de Leval, L., Koch, U., Trumpp, A., Sakamoto, K., Beermann, F., & Radtke, F. (2018). AMPK promotes survival of c-Myc-positive melanoma cells by suppressing oxidative stress. EMBO Journal, 37(5), [e97673]. https://doi.org/10.15252/embj.201797673

Vancouver

Kfoury A, Armaro M, Collodet C, Sordet-Dessimoz J, Giner MP, Christen S et al. AMPK promotes survival of c-Myc-positive melanoma cells by suppressing oxidative stress. EMBO Journal. 2018 Mar 1;37(5). e97673. https://doi.org/10.15252/embj.201797673

Author

Kfoury, Alain ; Armaro, Marzia ; Collodet, Caterina ; Sordet-Dessimoz, Jessica ; Giner, Maria Pilar ; Christen, Stefan ; Moco, Sofia ; Leleu, Marion ; de Leval, Laurence ; Koch, Ute ; Trumpp, Andreas ; Sakamoto, Kei ; Beermann, Friedrich ; Radtke, Freddy. / AMPK promotes survival of c-Myc-positive melanoma cells by suppressing oxidative stress. In: EMBO Journal. 2018 ; Vol. 37, No. 5.

Bibtex

@article{b094665b5111465586645d8b2e113c90,
title = "AMPK promotes survival of c-Myc-positive melanoma cells by suppressing oxidative stress",
abstract = "Although c-Myc is essential for melanocyte development, its role in cutaneous melanoma, the most aggressive skin cancer, is only partly understood. Here we used the NrasQ61KINK4a−/− mouse melanoma model to show that c-Myc is essential for tumor initiation, maintenance, and metastasis. c-Myc-expressing melanoma cells were preferentially found at metastatic sites, correlated with increased tumor aggressiveness and high tumor initiation potential. Abrogation of c-Myc caused apoptosis in primary murine and human melanoma cells. Mechanistically, c-Myc-positive melanoma cells activated and became dependent on the metabolic energy sensor AMP-activated protein kinase (AMPK), a metabolic checkpoint kinase that plays an important role in energy and redox homeostasis under stress conditions. AMPK pathway inhibition caused apoptosis of c-Myc-expressing melanoma cells, while AMPK activation protected against cell death of c-Myc-depleted melanoma cells through suppression of oxidative stress. Furthermore, TCGA database analysis of early-stage human melanoma samples revealed an inverse correlation between C-MYC and patient survival, suggesting that C-MYC expression levels could serve as a prognostic marker for early-stage disease.",
keywords = "AMPK, c-Myc, gene targeting, melanoma, oxidative stress",
author = "Alain Kfoury and Marzia Armaro and Caterina Collodet and Jessica Sordet-Dessimoz and Giner, {Maria Pilar} and Stefan Christen and Sofia Moco and Marion Leleu and {de Leval}, Laurence and Ute Koch and Andreas Trumpp and Kei Sakamoto and Friedrich Beermann and Freddy Radtke",
year = "2018",
month = mar,
day = "1",
doi = "10.15252/embj.201797673",
language = "English",
volume = "37",
journal = "E M B O Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "5",

}

RIS

TY - JOUR

T1 - AMPK promotes survival of c-Myc-positive melanoma cells by suppressing oxidative stress

AU - Kfoury, Alain

AU - Armaro, Marzia

AU - Collodet, Caterina

AU - Sordet-Dessimoz, Jessica

AU - Giner, Maria Pilar

AU - Christen, Stefan

AU - Moco, Sofia

AU - Leleu, Marion

AU - de Leval, Laurence

AU - Koch, Ute

AU - Trumpp, Andreas

AU - Sakamoto, Kei

AU - Beermann, Friedrich

AU - Radtke, Freddy

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Although c-Myc is essential for melanocyte development, its role in cutaneous melanoma, the most aggressive skin cancer, is only partly understood. Here we used the NrasQ61KINK4a−/− mouse melanoma model to show that c-Myc is essential for tumor initiation, maintenance, and metastasis. c-Myc-expressing melanoma cells were preferentially found at metastatic sites, correlated with increased tumor aggressiveness and high tumor initiation potential. Abrogation of c-Myc caused apoptosis in primary murine and human melanoma cells. Mechanistically, c-Myc-positive melanoma cells activated and became dependent on the metabolic energy sensor AMP-activated protein kinase (AMPK), a metabolic checkpoint kinase that plays an important role in energy and redox homeostasis under stress conditions. AMPK pathway inhibition caused apoptosis of c-Myc-expressing melanoma cells, while AMPK activation protected against cell death of c-Myc-depleted melanoma cells through suppression of oxidative stress. Furthermore, TCGA database analysis of early-stage human melanoma samples revealed an inverse correlation between C-MYC and patient survival, suggesting that C-MYC expression levels could serve as a prognostic marker for early-stage disease.

AB - Although c-Myc is essential for melanocyte development, its role in cutaneous melanoma, the most aggressive skin cancer, is only partly understood. Here we used the NrasQ61KINK4a−/− mouse melanoma model to show that c-Myc is essential for tumor initiation, maintenance, and metastasis. c-Myc-expressing melanoma cells were preferentially found at metastatic sites, correlated with increased tumor aggressiveness and high tumor initiation potential. Abrogation of c-Myc caused apoptosis in primary murine and human melanoma cells. Mechanistically, c-Myc-positive melanoma cells activated and became dependent on the metabolic energy sensor AMP-activated protein kinase (AMPK), a metabolic checkpoint kinase that plays an important role in energy and redox homeostasis under stress conditions. AMPK pathway inhibition caused apoptosis of c-Myc-expressing melanoma cells, while AMPK activation protected against cell death of c-Myc-depleted melanoma cells through suppression of oxidative stress. Furthermore, TCGA database analysis of early-stage human melanoma samples revealed an inverse correlation between C-MYC and patient survival, suggesting that C-MYC expression levels could serve as a prognostic marker for early-stage disease.

KW - AMPK

KW - c-Myc

KW - gene targeting

KW - melanoma

KW - oxidative stress

UR - http://www.scopus.com/inward/record.url?scp=85041919285&partnerID=8YFLogxK

U2 - 10.15252/embj.201797673

DO - 10.15252/embj.201797673

M3 - Journal article

C2 - 29440228

AN - SCOPUS:85041919285

VL - 37

JO - E M B O Journal

JF - E M B O Journal

SN - 0261-4189

IS - 5

M1 - e97673

ER -

ID: 238433940