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Article

AXL Controls Directed Migration of Mesenchymal Triple-Negative Breast Cancer Cells

by
Olivier Zajac
1,
Renaud Leclere
2,
André Nicolas
2,
Didier Meseure
2,
Caterina Marchiò
3,4,†,
Anne Vincent-Salomon
4,
Sergio Roman-Roman
5,
Marie Schoumacher
6 and
Thierry Dubois
1,*
1
Breast Cancer Biology Group, Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France
2
Department of Pathology, Platform of Investigative Pathology, Institut Curie, PSL Research University, 75005 Paris, France
3
Department of Medical Sciences, University of Turin, Via Verdi 8, 10124 Torino TO, Italy
4
Department of Pathology, Institut Curie, PSL Research University, 75005 Paris, France
5
Translational Research Department, Institut Curie, PSL Research University, 75005 Paris, France
6
Center for Therapeutic Innovation Oncology, Institut de Recherches Internationales SERVIER, 92284 Suresnes, France
*
Author to whom correspondence should be addressed.
†
Current affiliation: Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.
Cells 2020, 9(1), 247; https://doi.org/10.3390/cells9010247
Submission received: 23 December 2019 / Revised: 9 January 2020 / Accepted: 14 January 2020 / Published: 19 January 2020
(This article belongs to the Section Cell Motility and Adhesion)
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Abstract

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with high risk of relapse and metastasis. TNBC is a heterogeneous disease comprising different molecular subtypes including those with mesenchymal features. The tyrosine kinase AXL is expressed in mesenchymal cells and plays a role in drug resistance, migration and metastasis. We confirm that AXL is more expressed in mesenchymal TNBC cells compared to luminal breast cancer cells, and that its invalidation impairs cell migration while having no or little effect on cell viability. Here, we found that AXL controls directed migration. We observed that AXL displays a polarized localization at the Golgi apparatus and the leading edge of migratory mesenchymal TNBC cells. AXL co-localizes with F-actin at the front of the cells. In migratory polarized cells, the specific AXL inhibitor R428 displaces AXL and F-actin from the leading edge to a lateral area localized between the front and the rear of the cells where both are enriched in protrusions. In addition, R428 treatment disrupts the polarized localization of the Golgi apparatus towards the leading edge in migratory cells. Immunohistochemical analysis of aggressive chemo-resistant TNBC samples obtained before treatment reveals inter- and intra-tumor heterogeneity of the percentage of AXL expressing tumor cells, and a preference of these cells to be in contact with the stroma. Taken together, our study demonstrates that AXL controls directed cell migration most likely by regulating cell polarity.
Keywords: AXL; migration; polarity; triple-negative breast cancer; directionality; R428 AXL; migration; polarity; triple-negative breast cancer; directionality; R428

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MDPI and ACS Style

Zajac, O.; Leclere, R.; Nicolas, A.; Meseure, D.; Marchiò, C.; Vincent-Salomon, A.; Roman-Roman, S.; Schoumacher, M.; Dubois, T. AXL Controls Directed Migration of Mesenchymal Triple-Negative Breast Cancer Cells. Cells 2020, 9, 247. https://doi.org/10.3390/cells9010247

AMA Style

Zajac O, Leclere R, Nicolas A, Meseure D, Marchiò C, Vincent-Salomon A, Roman-Roman S, Schoumacher M, Dubois T. AXL Controls Directed Migration of Mesenchymal Triple-Negative Breast Cancer Cells. Cells. 2020; 9(1):247. https://doi.org/10.3390/cells9010247

Chicago/Turabian Style

Zajac, Olivier, Renaud Leclere, André Nicolas, Didier Meseure, Caterina Marchiò, Anne Vincent-Salomon, Sergio Roman-Roman, Marie Schoumacher, and Thierry Dubois. 2020. "AXL Controls Directed Migration of Mesenchymal Triple-Negative Breast Cancer Cells" Cells 9, no. 1: 247. https://doi.org/10.3390/cells9010247

APA Style

Zajac, O., Leclere, R., Nicolas, A., Meseure, D., Marchiò, C., Vincent-Salomon, A., Roman-Roman, S., Schoumacher, M., & Dubois, T. (2020). AXL Controls Directed Migration of Mesenchymal Triple-Negative Breast Cancer Cells. Cells, 9(1), 247. https://doi.org/10.3390/cells9010247

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