Reference : The TAT-RasGAP317-326 anti-cancer peptide can kill in a caspase-, apoptosis-, and nec...

	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	Focus Areas :	Systems Biomedicine
	To cite this reference:	http://hdl.handle.net/10993/32323

Title :	The TAT-RasGAP317-326 anti-cancer peptide can kill in a caspase-, apoptosis-, and necroptosis-independent manner
Language :	English
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]
Publication date :	27-Sep-2016
Journal title :	Oncotarget
Publisher :	Impact Journals
Volume :	7
Issue/season :	39
Peer reviewed :	Yes
Audience :	International
e-ISSN :	1949-2553
City :	Albany
Country :	NY
Keywords :	[en] 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 centres :	University of Lausanne
Funders :	Swiss National Science Foundation ; Swiss South African Joint Research Programme ; Swiss Cancer League grant n°KFS - 02543-02-2010 ; MD-PhD fellowship from the Swiss National Science Foundation
Target :	Researchers
Permalink :	http://hdl.handle.net/10993/32323
DOI :	10.18632/oncotarget.11841

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