Deciphering the molecular basis of invasiveness in Sdhb-deficient cells.

Détails

ID Serval
serval:BIB_4BA864F90F17
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Deciphering the molecular basis of invasiveness in Sdhb-deficient cells.
Périodique
Oncotarget
Auteur(s)
Loriot C., Domingues M., Berger A., Menara M., Ruel M., Morin A., Castro-Vega L.J., Letouzé É., Martinelli C., Bemelmans A.P., Larue L., Gimenez-Roqueplo A.P., Favier J.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Statut éditorial
Publié
Date de publication
20/10/2015
Peer-reviewed
Oui
Volume
6
Numéro
32
Pages
32955-32965
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Metastatic pheochromocytomas and paragangliomas (PPGL) are malignant neuroendocrine tumors frequently associated with germline mutations in the SDHB gene. SDHB-mutated PPGL display a hypermethylator phenotype associated with hallmarks of epithelial-to-mesenchymal transition (EMT). In the present study, we report the characterization of a unique model of Sdhb knockout in mouse chromaffin cells. Sdhb deficient cells exhibit a metastatic phenotype as highlighted by increased individual cell migration (characterized by faster motility and increased persistence) as well as high invasive and adhesion abilities. This phenotype is associated with the modulation of Twist1, Twist2, Tcf3, Snai1, N-cadherin or Krt19 expression, reflecting an EMT-like reprogramming of cells. Krt19 is epigenetically silenced in Sdhb-deficient cells and re-expressed after treatment by the demethylating agent decitabine. Krt19 rescue by lentiviral transduction in Sdhb-deficient cells and Krt19 inhibition by RNA interference in wild-type cells were performed. Both studies revealed the involvement of KRT19 in the invasive phenotype by modulating collective and individual migration and cell/extra-cellular matrix adhesion properties. These findings underline the role of hypermethylation and EMT in the in vitro acquisition of metastatic properties, following SDHB loss of function.
Mots-clé
Adrenal Gland Neoplasms/genetics, Adrenal Gland Neoplasms/metabolism, Animals, Cell Adhesion/physiology, Cell Line, Tumor, Chromaffin Cells/metabolism, Chromaffin Cells/pathology, Epithelial-Mesenchymal Transition, Humans, Mice, Mice, Knockout, Neoplasm Invasiveness, Neoplasm Metastasis, Paraganglioma/genetics, Paraganglioma/metabolism, Pheochromocytoma/genetics, Pheochromocytoma/metabolism, Succinate Dehydrogenase/deficiency, Succinate Dehydrogenase/genetics, Succinate Dehydrogenase/metabolism, Transcriptome, EMT, SDHB, keratin 19, metastasis, paraganglioma
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/07/2020 10:05
Dernière modification de la notice
16/07/2020 8:43
Données d'usage