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The Receptor Tyrosine Kinase AXL Is Required at Multiple Steps of the Metastatic Cascade During HER2-Positive Breast Cancer Progression

51 Pages Posted: 11 Apr 2018 Sneak Peek Status: Published

See all articles by Marie-Anne Goyette

Marie-Anne Goyette

Institut de Recherches Cliniques de Montreal (IRCM)

Stéphanie Duhamel

Institut de Recherches Cliniques de Montreal (IRCM)

Léo Aubert

University of Montreal - Institute for Research in Immunology and Cancer (IRIC)

Ariane Pelletier

Institut de Recherches Cliniques de Montreal (IRCM)

Paul Savage

McGill University - Rosalind and Morris Goodman Cancer Research Centre

Marie-Pier Thibault

Institut de Recherches Cliniques de Montreal (IRCM)

Radia Marie Johnson

McGill University - Rosalind and Morris Goodman Cancer Research Centre

Peter Carmeliet

University of Leuven - Laboratory of Angiogenesis and Vascular Metabolism

Mark Basik

McGill University - Department of Oncology and Surgery

Louis Gaboury

University of Montreal - Department of Pathology and Cell Biology

William J. Muller

McGill University - Rosalind and Morris Goodman Cancer Research Centre

Morag Park

McGill University - Rosalind and Morris Goodman Cancer Research Centre

Philippe P. Roux

University of Montreal - Institute for Research in Immunology and Cancer (IRIC)

Jean-Philippe Gratton

University of Montreal - Department of Pharmacology and Physiology

Jean-François Côté

Institut de Recherches Cliniques de Montreal (IRCM)

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Abstract

AXL is activated by its ligand GAS6 and is expressed in triple-negative breast cancer cells. In the current study, we report that AXL is also expressed in HER2 breast cancers where it correlates with poor patient survival. Using murine models of HER2 breast cancer, Axl, but not Gas6, was found to be essential for metastasis. We determined that AXL is required for intravasation, extravasation and growth at the metastatic site. AXL is expressed in HER2 cancers displaying EMT signatures where it contributes to sustained EMT. Interfering with AXL in a patient-derived xenograft impaired TGF-β-induced cell invasion. Lastly, pharmacological inhibition of AXL decreased the metastatic burden of mice developing HER2 breast cancer. Our data identify AXL as a potential anti-metastatic, co-therapeutic target for the treatment of HER2 breast cancers.

Suggested Citation

Goyette, Marie-Anne and Duhamel, Stéphanie and Aubert, Léo and Pelletier, Ariane and Savage, Paul and Thibault, Marie-Pier and Johnson, Radia Marie and Carmeliet, Peter and Basik, Mark and Gaboury, Louis and Muller, William J. and Park, Morag and Roux, Philippe P. and Gratton, Jean-Philippe and Côté, Jean-François, The Receptor Tyrosine Kinase AXL Is Required at Multiple Steps of the Metastatic Cascade During HER2-Positive Breast Cancer Progression (2018). Available at SSRN: https://ssrn.com/abstract=3155728 or http://dx.doi.org/10.2139/ssrn.3155728
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Marie-Anne Goyette

Institut de Recherches Cliniques de Montreal (IRCM)

Montreal, Quebec H2W 1R7
Canada

Stéphanie Duhamel

Institut de Recherches Cliniques de Montreal (IRCM)

Montreal, Quebec H2W 1R7
Canada

Léo Aubert

University of Montreal - Institute for Research in Immunology and Cancer (IRIC)

2900 Édouard-Montpetit Blvd.
Montreal, Quebec H3T 1J4
Canada

Ariane Pelletier

Institut de Recherches Cliniques de Montreal (IRCM)

Montreal, Quebec H2W 1R7
Canada

Paul Savage

McGill University - Rosalind and Morris Goodman Cancer Research Centre

1001 Sherbrooke St. W
Montreal, Quebec H3A 1G5
Canada

Marie-Pier Thibault

Institut de Recherches Cliniques de Montreal (IRCM)

Montreal, Quebec H2W 1R7
Canada

Radia Marie Johnson

McGill University - Rosalind and Morris Goodman Cancer Research Centre

1001 Sherbrooke St. W
Montreal, Quebec H3A 1G5
Canada

Peter Carmeliet

University of Leuven - Laboratory of Angiogenesis and Vascular Metabolism

Celestijnenlaan 200F
B-3001
Leuven
Belgium

Mark Basik

McGill University - Department of Oncology and Surgery

5750 Côte-des-Neiges Rd
Montreal, QC H3S 1Y9
Canada

Louis Gaboury

University of Montreal - Department of Pathology and Cell Biology

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

William J. Muller

McGill University - Rosalind and Morris Goodman Cancer Research Centre

1001 Sherbrooke St. W
Montreal, Quebec H3A 1G5
Canada

Morag Park

McGill University - Rosalind and Morris Goodman Cancer Research Centre

1001 Sherbrooke St. W
Montreal, Quebec H3A 1G5
Canada

Philippe P. Roux

University of Montreal - Institute for Research in Immunology and Cancer (IRIC)

2900 Édouard-Montpetit Blvd.
Montreal, Quebec H3T 1J4
Canada

Jean-Philippe Gratton

University of Montreal - Department of Pharmacology and Physiology

C.P. 6128 succursale Centre-ville
Montreal, Quebec H3C 3J7
Canada

Jean-François Côté (Contact Author)

Institut de Recherches Cliniques de Montreal (IRCM) ( email )

Montreal, Quebec H2W 1R7
Canada

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