Article (Scientific journals)
The TAT-RasGAP317-326 anti-cancer peptide can kill in a caspase-, apoptosis-, and necroptosis-independent manner
Heulot, Mathieu; Chevalier, Nadja; Puyal, Julien et al.
2016In Oncotarget, 7 (39)
Peer Reviewed verified by ORBi
 

Files


Full Text
The TAT-RasGAP_Impactjournals_2016.pdf
Publisher postprint (7.5 MB)
Request a copy

All documents in ORBilu are protected by a user license.

Send to



Details



Keywords :
tumor cell death; non-apoptotic death; cell-permeable peptides; RasGAP
Abstract :
[en] Tumor cell resistance to apoptosis, which is triggered by many anti-tumor therapies, remains a major clinical problem. Therefore, development of more efficient therapies is a priority to improve cancer prognosis. We have previously shown that a cell-permeable peptide derived from the p120 Ras GTPase-activating protein (RasGAP), called TAT-RasGAP317-326, bears anti-malignant activities in vitro and in vivo, such as inhibition of metastatic progression and tumor cell sensitization to cell death induced by various anti-cancer treatments. Recently, we discovered that this RasGAP-derived peptide possesses the ability to directly kill some cancer cells. TAT-RasGAP317-326 can cause cell death in a manner that can be either partially caspase-dependent or fully caspase-independent. Indeed, TAT-RasGAP317-326-induced toxicity was not or only partially prevented when apoptosis was inhibited. Moreover, blocking other forms of cell death, such as necroptosis, parthanatos, pyroptosis and autophagy did not hamper the killing activity of the peptide. The death induced by TAT-RasGAP317-326 can therefore proceed independently from these modes of death. Our finding has potentially interesting clinical relevance because activation of a death pathway that is distinct from apoptosis and necroptosis in tumor cells could lead to the generation of anti-cancer drugs that target pathways not yet considered for cancer treatment.
Research center :
University of Lausanne
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Heulot, Mathieu;  University of Lausanne > Department of Physiology
Chevalier, Nadja;  Université de Lausanne > 1Department of Physiology
Puyal, Julien;  Université de Lausanne > Department of Fundamental Neurosciences
Margue, Christiane  ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Michel, Sébastien;  Université de Lausanne > Department of Physiology
Kreis, Stephanie ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Kulms, Dagmar;  TU-Dresden > Department of Dermatology, Center for Regenerative Therapies
Barras, David;  Swiss Institute of Bioinformatics > Bioinformatics Core Facility
Nahimana, Aimable;  Centre Hospitalier Universitaire Vaudois (Lausanne) > Service and Central Laboratory of Hematology
Widmann, Christian;  Université de Lausanne > Department of Physiology
External co-authors :
yes
Language :
English
Title :
The TAT-RasGAP317-326 anti-cancer peptide can kill in a caspase-, apoptosis-, and necroptosis-independent manner
Publication date :
27 September 2016
Journal title :
Oncotarget
eISSN :
1949-2553
Publisher :
Impact Journals, Albany, United States - New York
Volume :
7
Issue :
39
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
Funders :
SNSF - Swiss National Science Foundation [CH]
Swiss South African Joint Research Programme
Swiss Cancer League grant n°KFS - 02543-02-2010
MD-PhD fellowship from the Swiss National Science Foundation
Available on ORBilu :
since 20 September 2017

Statistics


Number of views
65 (4 by Unilu)
Number of downloads
4 (2 by Unilu)

Scopus citations®
 
14
Scopus citations®
without self-citations
6
OpenCitations
 
18
WoS citations
 
16

Bibliography


Similar publications



Contact ORBilu