title: Asymmetric localisation of cytokine mRNA is essential for JAK/STAT activation during cell invasiveness.
abstract: The transition from immotile epithelial cells to migrating cells occurs in all organisms during normal embryonic development, as well as during tumour metastasis. During Drosophila oogenesis, border cells (BCs) are recruited and delaminate from the follicular epithelium. This process is triggered by the polar cells (PCs), which secrete the cytokine Unpaired (Upd) and activate the JAK/STAT pathway in neighbouring cells, turning them into invasive BCs. Interestingly, either a decrease or an increase in BC number alters migration, indicating that mechanisms controlling the level of JAK/STAT signalling are crucial in this process. Here, we show that PCs have a highly stable and polarised network of microtubules along which upd transcripts are asymmetrically transported in a Dynein-dependent manner. We demonstrate that in the absence of upd mRNA localisation the ligand is no longer efficiently secreted, leading to a loss of signalling strength as well as recruitment and migration defects. These findings reveal a novel post-transcriptional regulatory mechanism of JAK/STAT signalling in the control of epithelial cell invasiveness.
authors.affiliation: Institute of Developmental Biology and Cancer UMR6543/CNRS, University of Nice Sophia-Antipolis, Parc Valrose, 06108 Nice cedex 2, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Van de Bor
authors.forename: Geordie
authors.initials: G
authors.lastname: Zimniak
authors.forename: Delphine
authors.initials: D
authors.lastname: Cérézo
authors.forename: Sébastien
authors.initials: S
authors.lastname: Schaub
authors.forename: Stéphane
authors.initials: S
authors.lastname: Noselli
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D009866:Oogenesis / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D029721:Drosophila Proteins; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D014157:Transcription Factors; C115570:upd1 protein, Drosophila; D053612:Janus Kinases