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Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer

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Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer. / Bosurgi, Lidia; Bernink, Jochem H; Delgado Cuevas, Victor; Gagliani, Nicola; Joannas, Leonel; Schmid, Edward T; Booth, Carmen J; Ghosh, Sourav; Rothlin, Carla V.

in: P NATL ACAD SCI USA, Jahrgang 110, Nr. 32, 06.08.2013, S. 13091-6.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Bosurgi, L, Bernink, JH, Delgado Cuevas, V, Gagliani, N, Joannas, L, Schmid, ET, Booth, CJ, Ghosh, S & Rothlin, CV 2013, 'Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer', P NATL ACAD SCI USA, Jg. 110, Nr. 32, S. 13091-6. https://doi.org/10.1073/pnas.1302507110

APA

Bosurgi, L., Bernink, J. H., Delgado Cuevas, V., Gagliani, N., Joannas, L., Schmid, E. T., Booth, C. J., Ghosh, S., & Rothlin, C. V. (2013). Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer. P NATL ACAD SCI USA, 110(32), 13091-6. https://doi.org/10.1073/pnas.1302507110

Vancouver

Bosurgi L, Bernink JH, Delgado Cuevas V, Gagliani N, Joannas L, Schmid ET et al. Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer. P NATL ACAD SCI USA. 2013 Aug 6;110(32):13091-6. https://doi.org/10.1073/pnas.1302507110

Bibtex

@article{9f3791a749d94ffebb2f9bc6d195e9ce,
title = "Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer",
abstract = "The receptor tyrosine kinases Axl and Mer, belonging to the Tyro3, Axl and Mer (TAM) receptor family, are expressed in a number of tumor cells and have well-characterized oncogenic roles. The therapeutic targeting of these kinases is considered an anticancer strategy, and various inhibitors are currently under development. At the same time, Axl and Mer are expressed in dendritic cells and macrophages and have an essential function in limiting inflammation. Inflammation is an enabling characteristic of multiple cancer hallmarks. These contrasting oncogenic and anti-inflammatory functions of Axl and Mer posit a potential paradox in terms of anticancer therapy. Here we demonstrate that azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced inflammation-associated cancer is exacerbated in mice lacking Axl and Mer. Ablation of Axl and Mer signaling is associated with increased production of proinflammatory cytokines and failure to clear apoptotic neutrophils in the intestinal lamina propria, thereby favoring a tumor-promoting environment. Interestingly, loss of these genes in the hematopoietic compartment is not associated with increased colitis. Axl and Mer are expressed in radioresistant intestinal macrophages, and the loss of these genes is associated with an increased inflammatory signature in this compartment. Our results raise the possibility of potential adverse effects of systemic anticancer therapies with Axl and Mer inhibitors, and underscore the importance of understanding their tissue and cell type-specific functions in cancer.",
keywords = "Animals, Apoptosis, Azoxymethane, Colitis, Colon, Colonic Neoplasms, Cytokines, Dextran Sulfate, Female, Flow Cytometry, Gene Expression, Macrophages, Male, Mice, Mice, Inbred Strains, Mice, Knockout, Mucous Membrane, Neutrophils, Phagocytosis, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, c-Mer Tyrosine Kinase, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.",
author = "Lidia Bosurgi and Bernink, {Jochem H} and {Delgado Cuevas}, Victor and Nicola Gagliani and Leonel Joannas and Schmid, {Edward T} and Booth, {Carmen J} and Sourav Ghosh and Rothlin, {Carla V}",
year = "2013",
month = aug,
day = "6",
doi = "10.1073/pnas.1302507110",
language = "English",
volume = "110",
pages = "13091--6",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "32",

}

RIS

TY - JOUR

T1 - Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer

AU - Bosurgi, Lidia

AU - Bernink, Jochem H

AU - Delgado Cuevas, Victor

AU - Gagliani, Nicola

AU - Joannas, Leonel

AU - Schmid, Edward T

AU - Booth, Carmen J

AU - Ghosh, Sourav

AU - Rothlin, Carla V

PY - 2013/8/6

Y1 - 2013/8/6

N2 - The receptor tyrosine kinases Axl and Mer, belonging to the Tyro3, Axl and Mer (TAM) receptor family, are expressed in a number of tumor cells and have well-characterized oncogenic roles. The therapeutic targeting of these kinases is considered an anticancer strategy, and various inhibitors are currently under development. At the same time, Axl and Mer are expressed in dendritic cells and macrophages and have an essential function in limiting inflammation. Inflammation is an enabling characteristic of multiple cancer hallmarks. These contrasting oncogenic and anti-inflammatory functions of Axl and Mer posit a potential paradox in terms of anticancer therapy. Here we demonstrate that azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced inflammation-associated cancer is exacerbated in mice lacking Axl and Mer. Ablation of Axl and Mer signaling is associated with increased production of proinflammatory cytokines and failure to clear apoptotic neutrophils in the intestinal lamina propria, thereby favoring a tumor-promoting environment. Interestingly, loss of these genes in the hematopoietic compartment is not associated with increased colitis. Axl and Mer are expressed in radioresistant intestinal macrophages, and the loss of these genes is associated with an increased inflammatory signature in this compartment. Our results raise the possibility of potential adverse effects of systemic anticancer therapies with Axl and Mer inhibitors, and underscore the importance of understanding their tissue and cell type-specific functions in cancer.

AB - The receptor tyrosine kinases Axl and Mer, belonging to the Tyro3, Axl and Mer (TAM) receptor family, are expressed in a number of tumor cells and have well-characterized oncogenic roles. The therapeutic targeting of these kinases is considered an anticancer strategy, and various inhibitors are currently under development. At the same time, Axl and Mer are expressed in dendritic cells and macrophages and have an essential function in limiting inflammation. Inflammation is an enabling characteristic of multiple cancer hallmarks. These contrasting oncogenic and anti-inflammatory functions of Axl and Mer posit a potential paradox in terms of anticancer therapy. Here we demonstrate that azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced inflammation-associated cancer is exacerbated in mice lacking Axl and Mer. Ablation of Axl and Mer signaling is associated with increased production of proinflammatory cytokines and failure to clear apoptotic neutrophils in the intestinal lamina propria, thereby favoring a tumor-promoting environment. Interestingly, loss of these genes in the hematopoietic compartment is not associated with increased colitis. Axl and Mer are expressed in radioresistant intestinal macrophages, and the loss of these genes is associated with an increased inflammatory signature in this compartment. Our results raise the possibility of potential adverse effects of systemic anticancer therapies with Axl and Mer inhibitors, and underscore the importance of understanding their tissue and cell type-specific functions in cancer.

KW - Animals

KW - Apoptosis

KW - Azoxymethane

KW - Colitis

KW - Colon

KW - Colonic Neoplasms

KW - Cytokines

KW - Dextran Sulfate

KW - Female

KW - Flow Cytometry

KW - Gene Expression

KW - Macrophages

KW - Male

KW - Mice

KW - Mice, Inbred Strains

KW - Mice, Knockout

KW - Mucous Membrane

KW - Neutrophils

KW - Phagocytosis

KW - Proto-Oncogene Proteins

KW - Receptor Protein-Tyrosine Kinases

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Signal Transduction

KW - c-Mer Tyrosine Kinase

KW - Journal Article

KW - Research Support, N.I.H., Extramural

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

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

U2 - 10.1073/pnas.1302507110

DO - 10.1073/pnas.1302507110

M3 - SCORING: Journal article

C2 - 23878224

VL - 110

SP - 13091

EP - 13096

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 32

ER -