E4F1 dysfunction results in autophagic cell death in myeloid leukemic cells. - Archive ouverte HAL Access content directly
Journal Articles Autophagy Year : 2011

E4F1 dysfunction results in autophagic cell death in myeloid leukemic cells.

(1) , (1, 2) , (1) , (1)
1
2

Abstract

The multifunctional E4F1 protein was originally identified as a cellular target of the E1A adenoviral oncoprotein. Although E4F1 is implicated in several key oncogenic pathways, its roles in tumorigenesis remain unclear. Using a genetically engineered mouse model of myeloid leukemia (histiocytic sarcomas, HS) based on the genetic inactivation of the tumor suppressor Ink4a/Arf locus, we have recently unraveled an unsuspected function of E4F1 in the survival of leukemic cells. In vivo, genetic ablation of E4F1 in established myeloid tumors results in tumor regression. E4F1 inactivation results in a cascade of alterations originating from dysfunctional mitochondria that induce increased reactive oxygen species (ROS) levels and ends in massive autophagic cell death in HS transformed, but not normal myeloid cells. E4F1 depletion also induces cell death in various human myeloid leukemic cell lines, including acute myeloid leukemic (AML) cell lines. Interestingly, the E4F1 protein is overexpressed in a large proportion of human AML samples. These data provide new insights into E4F1-associated survival functions implicated in tumorigenesis and could open the path for new therapeutic strategies.
Fichier principal
Vignette du fichier
inserm-00646349_edited.pdf (90.1 Ko) Télécharger le fichier
Vignette du fichier
Hatchi_et_al_autophagy_2011.pdf (71.09 Ko) Télécharger le fichier
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)

Dates and versions

inserm-00646349 , version 1 (19-03-2012)

Identifiers

Cite

Elodie Hatchi, Laurent Le Cam, Geneviève Rodier, Claude Sardet. E4F1 dysfunction results in autophagic cell death in myeloid leukemic cells.. Autophagy, 2011, 7 (12), pp.1566-7. ⟨10.4161/auto.7.12.17991⟩. ⟨inserm-00646349⟩
216 View
499 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More