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Epitranscriptomics & Cancer Adaptation : A.David

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Our research work focuses on the contribution of post-transcriptional mechanisms on cancer cell adaptation, in particular RNA epigenetic & translational control.

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Group name EquipeELC
Item Type Journal Article
Title Secretion of IL1 by Dedifferentiated Melanoma Cells Inhibits JAK1-STAT3-Driven Actomyosin Contractility of Lymph Node Fibroblastic Reticular Cells
Creator Rovera et al.
Author Christopher Rovera
Author Ilona Berestjuk
Author Margaux Lecacheur
Author Cassandre Tavernier
Author Serena Diazzi
Author Sabrina Pisano
Author Marie Irondelle
Author Aude Mallavialle
Author Jean Albrengues
Author Cédric Gaggioli
Author Christophe A. Girard
Author Thierry Passeron
Author Marcel Deckert
Author Sophie Tartare-Deckert
Abstract Fibroblastic reticular cells (FRC) are immunologically specialized myofibroblasts that control the elasticity of the lymph node, in part through their contractile properties. Swelling of tumor-draining lymph nodes is a hallmark of lymphophilic cancers such as cutaneous melanoma. Melanoma displays high intratumoral heterogeneity with the coexistence of melanoma cells with variable differentiation phenotypes from melanocytic to dedifferentiated states. Factors secreted by melanoma cells promote premetastatic lymph node reprograming and tumor spreading. Elucidating the impact of the melanoma secretome on FRC could help identify approaches to prevent metastasis. Here we show that melanocytic and dedifferentiated melanoma cells differentially impact the FRC contractile phenotype. Factors secreted by dedifferentiated cells, but not by melanocytic cells, strongly inhibited actomyosin-dependent contractile forces of FRC by decreasing the activity of the RHOA-RHO-kinase (ROCK) pathway and the mechano-responsive transcriptional coactivator Yes1 associated transcriptional regulator (YAP). Transcriptional profiling and biochemical analyses indicated that actomyosin cytoskeleton relaxation in FRC is driven by inhibition of the JAK1-STAT3 pathway. This FRC relaxation was associated with increased FRC proliferation and activation and with elevated tumor invasion in vitro. The secretome of dedifferentiated melanoma cells also modulated the biomechanical properties of distant lymph node in premetastatic mouse models. Finally, IL1 produced by dedifferentiated cells was involved in the inhibition of FRC contractility. These data highlight the role of the JAK1-STAT3 and YAP pathways in spontaneous contractility of resting FRC. They also suggest that dedifferentiated melanoma cells specifically target FRC biomechanical properties to favor tumor spreading in the premetastatic lymph node niche. Targeting this remote communication could be an effective strategy to prevent metastatic spread of the disease. SIGNIFICANCE: Communication between dedifferentiated melanoma cells and lymph node fibroblasts reprograms the biomechanical properties of the premetastatic lymph node niche to promote tumor invasion. See related commentary by Lund, p. 1692.
Publication Cancer Research
Volume 82
Issue 9
Pages 1774-1788
Date 2022-05-03
Journal Abbr Cancer Res
Language eng
DOI 10.1158/0008-5472.CAN-21-0501
ISSN 1538-7445
Library Catalog PubMed
Extra PMID: 35502542
Tags Actomyosin, Animals, Fibroblasts, Humans, Interleukin-1, Janus Kinase 1, Lymph Nodes, Melanoma, Mice, original, Skin Neoplasms, STAT3 Transcription Factor
Date Added 2022/07/19 - 12:02:29
Date Modified 2022/07/19 - 12:06:19
Notes and Attachments PubMed entry (Attachment)


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