Distinct Cellular Origins and Differentiation Process Account for Distinct Oncogenic and Clinical Behaviors of Leiomyosarcomas - Inria - Institut national de recherche en sciences et technologies du numérique Accéder directement au contenu
Article Dans Une Revue Cancers Année : 2023

Distinct Cellular Origins and Differentiation Process Account for Distinct Oncogenic and Clinical Behaviors of Leiomyosarcomas

Elodie Darbo
Laëtitia Gaston
  • Fonction : Auteur
Christine Chevreau
  • Fonction : Auteur
Binh Bui
  • Fonction : Auteur
Eberhard Stoeckle
  • Fonction : Auteur
Dominique Ranchere-Vince
  • Fonction : Auteur
Pierre Méeus
  • Fonction : Auteur
Philippe Terrier
  • Fonction : Auteur
Sophie Piperno-Neumann
  • Fonction : Auteur
Françoise Collin
  • Fonction : Auteur
Gonzague de Pinieux
  • Fonction : Auteur
Florence Duffaud
  • Fonction : Auteur

Résumé

In leiomyosarcoma (LMS), a very aggressive disease, a relatively transcriptionally uniform subgroup of well-differentiated tumors has been described and is associated with poor survival. The question raised how differentiation and tumor progression, two apparently antagonist processes, coexist and allow tumor malignancy. We first identified the most transcriptionally homogeneous LMS subgroup in three independent cohorts, which we named ‘hLMS’. The integration of multi-omics data and functional analysis suggests that hLMS originate from vascular smooth muscle cells and show that hLMS transcriptional program reflects both modulations of smooth muscle contraction activity controlled by MYOCD/SRF regulatory network and activation of the cell cycle activity controlled by E2F/RB1 pathway. We propose that the phenotypic plasticity of vascular smooth muscle cells coupled with MYOCD/SRF pathway amplification, essential for hLMS survival, concomitant with PTEN absence and RB1 alteration, could explain how hLMS balance this uncommon interplay between differentiation and aggressiveness.

Domaines

Cancer

Dates et versions

hal-04094632 , version 1 (11-05-2023)

Identifiants

Citer

Elodie Darbo, Gaëlle Pérot, Lucie Darmusey, Sophie Le Guellec, Laura Leroy, et al.. Distinct Cellular Origins and Differentiation Process Account for Distinct Oncogenic and Clinical Behaviors of Leiomyosarcomas. Cancers, 2023, 15 (2), pp.534. ⟨10.3390/cancers15020534⟩. ⟨hal-04094632⟩
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