BTG1 inactivation drives lymphomagenesis and promotes lymphoma dissemination through activation of BCAR1.
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
09 03 2023
09 03 2023
Historique:
accepted:
01
11
2022
received:
04
05
2022
pubmed:
15
11
2022
medline:
14
3
2023
entrez:
14
11
2022
Statut:
ppublish
Résumé
Understanding the functional role of mutated genes in cancer is required to translate the findings of cancer genomics into therapeutic improvement. BTG1 is recurrently mutated in the MCD/C5 subtype of diffuse large B-cell lymphoma (DLBCL), which is associated with extranodal dissemination. Here, we provide evidence that Btg1 knock out accelerates the development of a lethal lymphoproliferative disease driven by Bcl2 overexpression. Furthermore, we show that the scaffolding protein BCAR1 is a BTG1 partner. Moreover, after BTG1 deletion or expression of BTG1 mutations observed in patients with DLBCL, the overactivation of the BCAR1-RAC1 pathway confers increased migration ability in vitro and in vivo. These modifications are targetable with the SRC inhibitor dasatinib, which opens novel therapeutic opportunities in BTG1 mutated DLBCL.
Identifiants
pubmed: 36375119
pii: S0006-4971(22)08069-7
doi: 10.1182/blood.2022016943
doi:
Substances chimiques
BTG1 protein, human
146835-72-5
Neoplasm Proteins
0
BCAR1 protein, human
0
Crk-Associated Substrate Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1209-1220Informations de copyright
© 2023 by The American Society of Hematology.