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Persistent DNA strand breaks induce a CAF-like phenotype in normal fibroblasts. / Legrand, Arnaud J.; Poletto, Mattia; Pankova, Daniela et al.

In: Oncotarget, Vol. 9, No. 17, 02.03.2018, p. 13666-13681.

Research output: Contribution to journal › Article › peer-review

Harvard

Legrand, AJ, Poletto, M, Pankova, D, Clementi, E, Moore, J, Castro-Giner, F, Ryan, AJ, O'Neill, E, Markkanen, E & Dianov, GL 2018, 'Persistent DNA strand breaks induce a CAF-like phenotype in normal fibroblasts', Oncotarget, vol. 9, no. 17, pp. 13666-13681. https://doi.org/10.18632/oncotarget.24446

APA

Legrand, A. J., Poletto, M., Pankova, D., Clementi, E., Moore, J., Castro-Giner, F., Ryan, A. J., O'Neill, E., Markkanen, E., & Dianov, G. L. (2018). Persistent DNA strand breaks induce a CAF-like phenotype in normal fibroblasts. Oncotarget, 9(17), 13666-13681. https://doi.org/10.18632/oncotarget.24446

Vancouver

Legrand AJ, Poletto M, Pankova D, Clementi E, Moore J, Castro-Giner F et al. Persistent DNA strand breaks induce a CAF-like phenotype in normal fibroblasts. Oncotarget. 2018 Mar 2;9(17):13666-13681. doi: 10.18632/oncotarget.24446

Author

Legrand, Arnaud J. ; Poletto, Mattia ; Pankova, Daniela et al. / Persistent DNA strand breaks induce a CAF-like phenotype in normal fibroblasts. In: Oncotarget. 2018 ; Vol. 9, No. 17. pp. 13666-13681.

BibTeX

@article{57ebddb5f45940cb96f5d6b0ccf4caaf,
title = "Persistent DNA strand breaks induce a CAF-like phenotype in normal fibroblasts",
abstract = "Cancer-associated fibroblasts (CAFs) are an emerging target for cancer therapy as they promote tumour growth and metastatic potential. However, CAF targeting is complicated by the lack of knowledge-based strategies aiming to selectively eliminate these cells. There is a growing body of evidence suggesting that a proinflammatory microenvironment (e.g. ROS and cytokines) promotes CAF formation during tumorigenesis, although the exact mechanisms involved remain unclear. In this study, we reveal that a prolonged pro-inflammatory stimulation causes a de facto deficiency in base excision repair, generating unrepaired DNA strand breaks and thereby triggering an ATF4-dependent reprogramming of normal fibroblasts into CAF-like cells. Based on the phenotype of in vitro-generated CAFs, we demonstrate that midostaurin, a clinically relevant compound, selectively eliminates CAF-like cells deficient in base excision repair and prevents their stimulatory role in cancer cell growth and migration.",
keywords = "Base excision repair, Cancer-associated fibroblasts, Midostaurin, Tumour microenvironment, Tumour stroma",
author = "Legrand, {Arnaud J.} and Mattia Poletto and Daniela Pankova and Elena Clementi and John Moore and Francesc Castro-Giner and Ryan, {Anderson J.} and Eric O'Neill and Enni Markkanen and Dianov, {Grigory L.}",
note = "Publisher Copyright: {\textcopyright} Legrand et al.",
year = "2018",
month = mar,
day = "2",
doi = "10.18632/oncotarget.24446",
language = "English",
volume = "9",
pages = "13666--13681",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "17",

}

RIS

TY - JOUR

T1 - Persistent DNA strand breaks induce a CAF-like phenotype in normal fibroblasts

AU - Legrand, Arnaud J.

AU - Poletto, Mattia

AU - Pankova, Daniela

AU - Clementi, Elena

AU - Moore, John

AU - Castro-Giner, Francesc

AU - Ryan, Anderson J.

AU - O'Neill, Eric

AU - Markkanen, Enni

AU - Dianov, Grigory L.

N1 - Publisher Copyright: © Legrand et al.

PY - 2018/3/2

Y1 - 2018/3/2

N2 - Cancer-associated fibroblasts (CAFs) are an emerging target for cancer therapy as they promote tumour growth and metastatic potential. However, CAF targeting is complicated by the lack of knowledge-based strategies aiming to selectively eliminate these cells. There is a growing body of evidence suggesting that a proinflammatory microenvironment (e.g. ROS and cytokines) promotes CAF formation during tumorigenesis, although the exact mechanisms involved remain unclear. In this study, we reveal that a prolonged pro-inflammatory stimulation causes a de facto deficiency in base excision repair, generating unrepaired DNA strand breaks and thereby triggering an ATF4-dependent reprogramming of normal fibroblasts into CAF-like cells. Based on the phenotype of in vitro-generated CAFs, we demonstrate that midostaurin, a clinically relevant compound, selectively eliminates CAF-like cells deficient in base excision repair and prevents their stimulatory role in cancer cell growth and migration.

AB - Cancer-associated fibroblasts (CAFs) are an emerging target for cancer therapy as they promote tumour growth and metastatic potential. However, CAF targeting is complicated by the lack of knowledge-based strategies aiming to selectively eliminate these cells. There is a growing body of evidence suggesting that a proinflammatory microenvironment (e.g. ROS and cytokines) promotes CAF formation during tumorigenesis, although the exact mechanisms involved remain unclear. In this study, we reveal that a prolonged pro-inflammatory stimulation causes a de facto deficiency in base excision repair, generating unrepaired DNA strand breaks and thereby triggering an ATF4-dependent reprogramming of normal fibroblasts into CAF-like cells. Based on the phenotype of in vitro-generated CAFs, we demonstrate that midostaurin, a clinically relevant compound, selectively eliminates CAF-like cells deficient in base excision repair and prevents their stimulatory role in cancer cell growth and migration.

KW - Base excision repair

KW - Cancer-associated fibroblasts

KW - Midostaurin

KW - Tumour microenvironment

KW - Tumour stroma

UR - http://www.scopus.com/inward/record.url?scp=85042723913&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.24446

DO - 10.18632/oncotarget.24446

M3 - Article

C2 - 29568385

AN - SCOPUS:85042723913

VL - 9

SP - 13666

EP - 13681

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 17

ER -

ID: 14280068