No full text
Poster (Scientific congresses and symposiums)
JNK/ROS signaling pathway is responsible for induction of autophagy in HDAC5 depleted cancer cells
Hendrick, Elodie; Matheus, Nicolas; Peixoto, Paul et al.
2013Giga Day 2013
 

Files


Full Text
No document available.

Send to



Details



Keywords :
HDAC5; Cancer; Apoptosis
Abstract :
[en] Introduction: Histone deacetylases (HDAC) is a family of eighteen enzymes which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that depletion of HDAC5 using siRNA technology triggered cancer cells to both autophagy and apoptosis (ref papier). The study of autophagy in cancer is a new research field that has recently generated tremendous attention due to the recognition that autophagy can have either pro-survival or pro-death functions depending on its level of activation. In addition, more and more studies indicate that a complex relationship exists between autophagy and apoptosis, and that the interplay between these two processes determines whether a cell will live or die. Aims: The goal of this study is to further understand the role of autophagy induced by HDAC5 depletion. Current investigations include determining the molecular mechanisms by which HDAC5 depletion induces autophagy and exploring regulatory relationship between autophagy and apoptosis on cancer cell death in absence of HDAC5. Results: The set up of the autophagy in absence of HDAC5 was demonstrated by the conversion of LC3 and development of autophagosomes by electronic microscopy. Transcriptomic study demonstrated a deregulation of a set of genes involved in ROS detoxification in HDAC5 depleted cancer cells leading to significant increase of ROS levels. Further investigations showed that pretreatment with NAC, a ROS scavenger, effectively blocked the accumulation of ROS and autopahgy triggered by HDAC5 silencing. Moreover, HDAC5 depletion induces activation of JNK, and knockdown of JNK by siRNA inhibited ROS production and autophagy, but antioxidant NAC failed to block JNK activation induced by HDAC5 depletion indicating that JNK activation may be a upstream signaling of ROS and should be a core component in HDAC5 silencing-induced autophagic signaling pathway. Finally, blocking of autophagy induced by HDAC5 silencing with NAC or chloroquine and bafilomycin enhanced pro-apoptotic effect. Conclusion: Autophagy functions as a prosurvival mechanism to mitigate HDAC5 depletion-induced apoptotic cell death, suggesting that targeting autophagy might improve the therapeutic effects of specific HDAC5 inhibition.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Hendrick, Elodie ;  Université de Liège > Département des sciences de la vie > Génétique et biologie moléculaires animales
Matheus, Nicolas 
Peixoto, Paul ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Polese, Catherine 
Thiry, Marc  
Mouithys-Mickalad, Ange ;  Université de Liège > Centre de l'oxygène : Recherche et développement (C.O.R.D.)
Serteyn, Didier  ;  Université de Liège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Anesthésiologie gén. et pathologie chirurg. des grds animaux
Castronovo, Vincenzo ;  Université de Liège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Language :
English
Title :
JNK/ROS signaling pathway is responsible for induction of autophagy in HDAC5 depleted cancer cells
Publication date :
28 January 2013
Number of pages :
A0
Event name :
Giga Day 2013
Event place :
Liège, Belgium
Event date :
du 28 janvier 2013 au 28 janvier 2013
By request :
Yes
Available on ORBi :
since 03 June 2015

Statistics


Number of views
35 (3 by ULiège)
Number of downloads
0 (0 by ULiège)

Bibliography


Similar publications



Contact ORBi