Distinct Cellular Origins and Differentiation Process Account for Distinct Oncogenic and Clinical Behaviors of Leiomyosarcomas.
Fiche publication
Date publication
janvier 2023
Journal
Cancers
Auteurs
Membres identifiés du Cancéropôle Est :
Dr COLLIN Françoise
Tous les auteurs :
Darbo E, Pérot G, Darmusey L, Le Guellec S, Leroy L, Gaston L, Desplat N, Thébault N, Merle C, Rochaix P, Valentin T, Ferron G, Chevreau C, Bui B, Stoeckle E, Ranchere-Vince D, Méeus P, Terrier P, Piperno-Neumann S, Collin F, De Pinieux G, Duffaud F, Coindre JM, Blay JY, Chibon F
Lien Pubmed
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 alteration, could explain how hLMS balance this uncommon interplay between differentiation and aggressiveness.
Mots clés
bioinformatics, differentiation, leiomyosarcoma, oncogenesis, transcriptional regulation
Référence
Cancers (Basel). 2023 01 15;15(2):