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.
Highlights
Triple negative breast cancer (TNBC) accounts for about 15% of breast cancers and is defined by the lack of expression of estrogen receptor (ER) and progesterone receptor (PR), and the absence ofHer2 overexpression [1,2]
We found that AXL is more expressed in mesenchymal Triple-negative breast cancer (TNBC) cells compared to the two luminal cell lines (Figure S1A) confirming previous studies [38]
TNBC is the breast cancer subtype associated with the worst prognosis due to high percentage of relapse andismetastases following treatment
Summary
Triple negative breast cancer (TNBC) accounts for about 15% of breast cancers and is defined by the lack of expression of estrogen receptor (ER) and progesterone receptor (PR), and the absence ofHer overexpression [1,2]. A pivotal challenge in the treatment of TNBC patients is their inter- and intra-tumor heterogeneity [3,4,5]. TNBC encompasses a heterogeneous group including tumors with a. The ability of some epithelial cells to acquire a mesenchymal phenotype is important during development and wound healing [11,12,13]. This cellular plasticity, called epithelial-to-mesenchymal transition (EMT), allowing the cells to gain new abilities to migrate and cross an extracellular matrix, is crucial for the metastatic process [14,15,16,17]. Cells undergoing EMT are less proliferative and more prone to resist to chemo- and targeted-therapies [18,19,20,21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
