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01.12.2013 | Original Research

Autocrine role for Gas6 with Tyro3 and Axl in leiomyosarcomas

verfasst von: Hiba el Sayadi, Daniel Pissaloux, Laurent Alberti, Severine Tabone-Eglinger, Dominique Ranchere, Anne Valérie Decouvelaere, Eric Tabone, Isabelle Ray-Coquard, Christophe Caux, Jérome Fayette, Jean-Yves Blay

Erschienen in: Targeted Oncology | Ausgabe 4/2013

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Abstract

Leiomyosarcoma (LMS) represent 15 % of adult sarcomas. The aim of this work was to identify novel altered pathways in LMS, which may be of therapeutic value for patients. Thirteen fresh frozen samples of soft tissue and visceral LMS were analyzed and compared with normal smooth muscle uterine tissue (NSM) for phosphoproteomic profile. Four proteins were found differentially expressed including Tyro3. The functional role of Tyro3 and its ligand Gas6 was investigated in two LMS cell lines, SK-LMS-1 and CNIO-AA. Four proteins and phosphoproteins were differentially expressed in LMS samples vs NSM: A loss of FAK Y397 phosphorylation was observed in all LMSs, while Tyro3, MSH2 and PKC theta were consistently overexpressed. Gas6, the major ligand of Tyro3, was expressed in 8 of the 13 LMS samples, and Gas6 expression highly correlated to Akt Y473 phosphorylation and to a lesser extent to Erk1/2 phosphorylation. SK-LMS-1 and CNIO-AA LMS expressed Tyro3, Axl and Gas6 at high level in CNIO-AA while at low levels in SK-LMS-1. Exposure of both cell lines to foretinib, a tyrosine kinase inhibitor of Met, Axl and Tyro3, reduced cell viability and induced caspase 3/7 activation. Transfection of CNIO-AA with small interfering RNA directed against Tyro3 and Axl genes induced a reduction of the expression of the specific proteins and, when combined, significantly reduced CNIO-AA cell viability. Leiomyosarcomas overexpress Tyro3. Gas6, a ligand of Tyro3, exerts an autocrine activities though Tyro3 and Axl in a subgroup of LMS.

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Titel: Autocrine role for Gas6 with Tyro3 and Axl in leiomyosarcomas
verfasst von: Hiba el Sayadi
Daniel Pissaloux
Laurent Alberti
Severine Tabone-Eglinger
Dominique Ranchere
Anne Valérie Decouvelaere
Eric Tabone
Isabelle Ray-Coquard
Christophe Caux
Jérome Fayette
Jean-Yves Blay
Publikationsdatum: 01.12.2013
Verlag: Springer Paris
Erschienen in: Targeted Oncology / Ausgabe 4/2013
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-012-0249-2

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Autocrine role for Gas6 with Tyro3 and Axl in leiomyosarcomas

Abstract

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Abstract

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