| Added by | pmartino |
|---|---|
| Group name | EquipePM |
| Item Type | Journal Article |
| Title | Upregulated flotillins and sphingosine kinase 2 derail AXL vesicular traffic to promote epithelial-mesenchymal transition |
| Creator | Genest et al. |
| Author | Mallory Genest |
| Author | Franck Comunale |
| Author | Damien Planchon |
| Author | Pauline Govindin |
| Author | Dune Noly |
| Author | Sophie Vacher |
| Author | Ivan Bièche |
| Author | Bruno Robert |
| Author | Himanshu Malhotra |
| Author | Andreas Schoenit |
| Author | Liubov A. Tashireva |
| Author | Josefina Casas |
| Author | Cécile Gauthier-Rouvière |
| Author | Stéphane Bodin |
| Abstract | Altered endocytosis and vesicular trafficking are major players during tumorigenesis. Flotillin overexpression, a feature observed in many invasive tumors and identified as a marker of poor prognosis, induces a deregulated endocytic and trafficking pathway called upregulated flotillin-induced trafficking (UFIT). Here, we found that in non-tumoral mammary epithelial cells, induction of the UFIT pathway promotes epithelial-to-mesenchymal transition (EMT) and accelerates the endocytosis of several transmembrane receptors, including AXL, in flotillin-positive late endosomes. AXL overexpression, frequently observed in cancer cells, is linked to EMT and metastasis formation. In flotillin-overexpressing non-tumoral mammary epithelial cells and in invasive breast carcinoma cells, we found that the UFIT pathway-mediated AXL endocytosis allows its stabilization and depends on sphingosine kinase 2, a lipid kinase recruited in flotillin-rich plasma membrane domains and endosomes. Thus, the deregulation of vesicular trafficking following flotillin upregulation, and through sphingosine kinase 2, emerges as a new mechanism of AXL overexpression and EMT-inducing signaling pathway activation. |
| Publication | Journal of Cell Science |
| Volume | 135 |
| Issue | 7 |
| Pages | jcs259178 |
| Date | 2022-04-01 |
| Journal Abbr | J Cell Sci |
| Language | eng |
| DOI | 10.1242/jcs.259178 |
| ISSN | 1477-9137 |
| Library Catalog | PubMed |
| Extra | PMID: 35394045 |
| Tags | AXL, Axl Receptor Tyrosine Kinase, Breast Neoplasms, Cell Line, Tumor, Endosomal trafficking, Epithelial to mesenchymal transition, Epithelial-Mesenchymal Transition, Female, Flotillins, Humans, Membrane Proteins, original, Phosphotransferases (Alcohol Group Acceptor), Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases, Sphingosine kinase 2 |
| Date Added | 2023/08/04 - 17:26:39 |
| Date Modified | 2023/08/04 - 17:30:01 |
| Notes and Attachments | Full Text (Attachment) PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
