Multidrug resistance protein 3 loss promotes tumor formation by inducing senescence escape

Clotilde Wiel, Baptiste Gras, David Vindrieux, M Warnier, Delphine Gitenay, B Le Calvé, Mylène Ferrand, Arnaud Augert, D. Bernard

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Oncogenic-stress-induced senescence (OIS) is a stress response allowing normal cells, when receiving oncogenic signals, to stably arrest their proliferation. OIS thus acts to prevent aberrant cell proliferation and tumor formation. To identify novel tumor suppressive pathways, we have recently completed a loss-of-function genetic screen to identify novel genes promoting escape from OIS and thus, potentially, tumor formation when their functions are lost. Using this approach, we unexpectedly found that loss of function of the multidrug resistance protein 3 (MRP3 or ABCC3) promotes escape from OIS in human epithelial cells. Importantly, ABCC3 expression is reduced in human skin tumors, and ABCC3-knockout mice display increased sensitivity to RAS-induced skin carcinogenesis, concomitantly with decreased OIS. ABCC3 participates in resistance to chemotherapy via its transporter activity. Our data show that this transporter activity is involved in ABCC3-induced senescence, demonstrating that this protein has a complex role in cancer, since its loss of function may promote escape from OIS and tumor formation whereas its gain of function promotes resistance to chemotherapy.

langue originaleAnglais
Pages (de - à)1596-601
Nombre de pages6
journalOncogene
Volume35
Numéro de publication12
Les DOIs
étatPublié - 2016
Modification externeOui

Empreinte digitale

Neoplasms
Drug Therapy
Skin
multidrug resistance protein 3
Knockout Mice
Carcinogenesis
Epithelial Cells
Cell Proliferation
Genes
Proteins

Citer ceci

Wiel, Clotilde ; Gras, Baptiste ; Vindrieux, David ; Warnier, M ; Gitenay, Delphine ; Le Calvé, B ; Ferrand, Mylène ; Augert, Arnaud ; Bernard, D. . / Multidrug resistance protein 3 loss promotes tumor formation by inducing senescence escape. Dans: Oncogene. 2016 ; Vol 35, Numéro 12. p. 1596-601.
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title = "Multidrug resistance protein 3 loss promotes tumor formation by inducing senescence escape",
abstract = "Oncogenic-stress-induced senescence (OIS) is a stress response allowing normal cells, when receiving oncogenic signals, to stably arrest their proliferation. OIS thus acts to prevent aberrant cell proliferation and tumor formation. To identify novel tumor suppressive pathways, we have recently completed a loss-of-function genetic screen to identify novel genes promoting escape from OIS and thus, potentially, tumor formation when their functions are lost. Using this approach, we unexpectedly found that loss of function of the multidrug resistance protein 3 (MRP3 or ABCC3) promotes escape from OIS in human epithelial cells. Importantly, ABCC3 expression is reduced in human skin tumors, and ABCC3-knockout mice display increased sensitivity to RAS-induced skin carcinogenesis, concomitantly with decreased OIS. ABCC3 participates in resistance to chemotherapy via its transporter activity. Our data show that this transporter activity is involved in ABCC3-induced senescence, demonstrating that this protein has a complex role in cancer, since its loss of function may promote escape from OIS and tumor formation whereas its gain of function promotes resistance to chemotherapy.",
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author = "Clotilde Wiel and Baptiste Gras and David Vindrieux and M Warnier and Delphine Gitenay and {Le Calv{\'e}}, B and Myl{\`e}ne Ferrand and Arnaud Augert and D. Bernard",
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Wiel, C, Gras, B, Vindrieux, D, Warnier, M, Gitenay, D, Le Calvé, B, Ferrand, M, Augert, A & Bernard, D 2016, 'Multidrug resistance protein 3 loss promotes tumor formation by inducing senescence escape', Oncogene, VOL. 35, Numéro 12, p. 1596-601. https://doi.org/10.1038/onc.2015.218

Multidrug resistance protein 3 loss promotes tumor formation by inducing senescence escape. / Wiel, Clotilde; Gras, Baptiste; Vindrieux, David; Warnier, M; Gitenay, Delphine; Le Calvé, B; Ferrand, Mylène; Augert, Arnaud; Bernard, D. .

Dans: Oncogene, Vol 35, Numéro 12, 2016, p. 1596-601.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - Multidrug resistance protein 3 loss promotes tumor formation by inducing senescence escape

AU - Wiel, Clotilde

AU - Gras, Baptiste

AU - Vindrieux, David

AU - Warnier, M

AU - Gitenay, Delphine

AU - Le Calvé, B

AU - Ferrand, Mylène

AU - Augert, Arnaud

AU - Bernard, D.

PY - 2016

Y1 - 2016

N2 - Oncogenic-stress-induced senescence (OIS) is a stress response allowing normal cells, when receiving oncogenic signals, to stably arrest their proliferation. OIS thus acts to prevent aberrant cell proliferation and tumor formation. To identify novel tumor suppressive pathways, we have recently completed a loss-of-function genetic screen to identify novel genes promoting escape from OIS and thus, potentially, tumor formation when their functions are lost. Using this approach, we unexpectedly found that loss of function of the multidrug resistance protein 3 (MRP3 or ABCC3) promotes escape from OIS in human epithelial cells. Importantly, ABCC3 expression is reduced in human skin tumors, and ABCC3-knockout mice display increased sensitivity to RAS-induced skin carcinogenesis, concomitantly with decreased OIS. ABCC3 participates in resistance to chemotherapy via its transporter activity. Our data show that this transporter activity is involved in ABCC3-induced senescence, demonstrating that this protein has a complex role in cancer, since its loss of function may promote escape from OIS and tumor formation whereas its gain of function promotes resistance to chemotherapy.

AB - Oncogenic-stress-induced senescence (OIS) is a stress response allowing normal cells, when receiving oncogenic signals, to stably arrest their proliferation. OIS thus acts to prevent aberrant cell proliferation and tumor formation. To identify novel tumor suppressive pathways, we have recently completed a loss-of-function genetic screen to identify novel genes promoting escape from OIS and thus, potentially, tumor formation when their functions are lost. Using this approach, we unexpectedly found that loss of function of the multidrug resistance protein 3 (MRP3 or ABCC3) promotes escape from OIS in human epithelial cells. Importantly, ABCC3 expression is reduced in human skin tumors, and ABCC3-knockout mice display increased sensitivity to RAS-induced skin carcinogenesis, concomitantly with decreased OIS. ABCC3 participates in resistance to chemotherapy via its transporter activity. Our data show that this transporter activity is involved in ABCC3-induced senescence, demonstrating that this protein has a complex role in cancer, since its loss of function may promote escape from OIS and tumor formation whereas its gain of function promotes resistance to chemotherapy.

KW - Animals

KW - Cells, Cultured

KW - Mice

KW - Neoplasms

KW - P-Glycoproteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/onc.2015.218

DO - 10.1038/onc.2015.218

M3 - Article

C2 - 26073088

VL - 35

SP - 1596

EP - 1601

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 12

ER -