Deep Proteomics of Breast Cancer Cells Reveals that Metformin Rewires Signaling Networks Away from a Pro-growth State

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

Standard

Deep Proteomics of Breast Cancer Cells Reveals that Metformin Rewires Signaling Networks Away from a Pro-growth State. / Sacco, Francesca; Silvestri, Alessandra; Posca, Daniela; Pirrò, Stefano; Gherardini, Pier Federico; Castagnoli, Luisa; Mann, Matthias; Cesareni, Gianni.

In: Cell Systems, Vol. 2, No. 3, 23.03.2016, p. 159-71.

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

Harvard

Sacco, F, Silvestri, A, Posca, D, Pirrò, S, Gherardini, PF, Castagnoli, L, Mann, M & Cesareni, G 2016, 'Deep Proteomics of Breast Cancer Cells Reveals that Metformin Rewires Signaling Networks Away from a Pro-growth State', Cell Systems, vol. 2, no. 3, pp. 159-71. https://doi.org/10.1016/j.cels.2016.02.005

APA

Sacco, F., Silvestri, A., Posca, D., Pirrò, S., Gherardini, P. F., Castagnoli, L., Mann, M., & Cesareni, G. (2016). Deep Proteomics of Breast Cancer Cells Reveals that Metformin Rewires Signaling Networks Away from a Pro-growth State. Cell Systems, 2(3), 159-71. https://doi.org/10.1016/j.cels.2016.02.005

Vancouver

Sacco F, Silvestri A, Posca D, Pirrò S, Gherardini PF, Castagnoli L et al. Deep Proteomics of Breast Cancer Cells Reveals that Metformin Rewires Signaling Networks Away from a Pro-growth State. Cell Systems. 2016 Mar 23;2(3):159-71. https://doi.org/10.1016/j.cels.2016.02.005

Author

Sacco, Francesca ; Silvestri, Alessandra ; Posca, Daniela ; Pirrò, Stefano ; Gherardini, Pier Federico ; Castagnoli, Luisa ; Mann, Matthias ; Cesareni, Gianni. / Deep Proteomics of Breast Cancer Cells Reveals that Metformin Rewires Signaling Networks Away from a Pro-growth State. In: Cell Systems. 2016 ; Vol. 2, No. 3. pp. 159-71.

Bibtex

@article{e4c530f0bf794675b07f3fe2792141c0,
title = "Deep Proteomics of Breast Cancer Cells Reveals that Metformin Rewires Signaling Networks Away from a Pro-growth State",
abstract = "Metformin is the most frequently prescribed drug for type 2 diabetes. In addition to its hypoglycemic effects, metformin also lowers cancer incidence. This anti-cancer activity is incompletely understood. Here, we profiled the metformin-dependent changes in the proteome and phosphoproteome of breast cancer cells using high-resolution mass spectrometry. In total, we quantified changes of 7,875 proteins and 15,813 phosphosites after metformin changes. To interpret these datasets, we developed a generally applicable strategy that overlays metformin-dependent changes in the proteome and phosphoproteome onto a literature-derived network. This approach suggested that metformin treatment makes cancer cells more sensitive to apoptotic stimuli and less sensitive to pro-growth stimuli. These hypotheses were tested in vivo; as a proof-of-principle, we demonstrated that metformin inhibits the p70S6K-rpS6 axis in a PP2A-phosphatase dependent manner. In conclusion, analysis of deep proteomics reveals both detailed and global mechanisms that contribute to the anti-cancer activity of metformin.",
keywords = "Journal Article",
author = "Francesca Sacco and Alessandra Silvestri and Daniela Posca and Stefano Pirr{\`o} and Gherardini, {Pier Federico} and Luisa Castagnoli and Matthias Mann and Gianni Cesareni",
note = "Copyright {\textcopyright} 2016 Elsevier Inc. All rights reserved.",
year = "2016",
month = mar,
day = "23",
doi = "10.1016/j.cels.2016.02.005",
language = "English",
volume = "2",
pages = "159--71",
journal = "Cell Systems",
issn = "2405-4712",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - Deep Proteomics of Breast Cancer Cells Reveals that Metformin Rewires Signaling Networks Away from a Pro-growth State

AU - Sacco, Francesca

AU - Silvestri, Alessandra

AU - Posca, Daniela

AU - Pirrò, Stefano

AU - Gherardini, Pier Federico

AU - Castagnoli, Luisa

AU - Mann, Matthias

AU - Cesareni, Gianni

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/3/23

Y1 - 2016/3/23

N2 - Metformin is the most frequently prescribed drug for type 2 diabetes. In addition to its hypoglycemic effects, metformin also lowers cancer incidence. This anti-cancer activity is incompletely understood. Here, we profiled the metformin-dependent changes in the proteome and phosphoproteome of breast cancer cells using high-resolution mass spectrometry. In total, we quantified changes of 7,875 proteins and 15,813 phosphosites after metformin changes. To interpret these datasets, we developed a generally applicable strategy that overlays metformin-dependent changes in the proteome and phosphoproteome onto a literature-derived network. This approach suggested that metformin treatment makes cancer cells more sensitive to apoptotic stimuli and less sensitive to pro-growth stimuli. These hypotheses were tested in vivo; as a proof-of-principle, we demonstrated that metformin inhibits the p70S6K-rpS6 axis in a PP2A-phosphatase dependent manner. In conclusion, analysis of deep proteomics reveals both detailed and global mechanisms that contribute to the anti-cancer activity of metformin.

AB - Metformin is the most frequently prescribed drug for type 2 diabetes. In addition to its hypoglycemic effects, metformin also lowers cancer incidence. This anti-cancer activity is incompletely understood. Here, we profiled the metformin-dependent changes in the proteome and phosphoproteome of breast cancer cells using high-resolution mass spectrometry. In total, we quantified changes of 7,875 proteins and 15,813 phosphosites after metformin changes. To interpret these datasets, we developed a generally applicable strategy that overlays metformin-dependent changes in the proteome and phosphoproteome onto a literature-derived network. This approach suggested that metformin treatment makes cancer cells more sensitive to apoptotic stimuli and less sensitive to pro-growth stimuli. These hypotheses were tested in vivo; as a proof-of-principle, we demonstrated that metformin inhibits the p70S6K-rpS6 axis in a PP2A-phosphatase dependent manner. In conclusion, analysis of deep proteomics reveals both detailed and global mechanisms that contribute to the anti-cancer activity of metformin.

KW - Journal Article

U2 - 10.1016/j.cels.2016.02.005

DO - 10.1016/j.cels.2016.02.005

M3 - Journal article

C2 - 27135362

VL - 2

SP - 159

EP - 171

JO - Cell Systems

JF - Cell Systems

SN - 2405-4712

IS - 3

ER -

ID: 186876945