Reference : The TAT-RasGAP317-326 anti-cancer peptide can kill in a caspase-, apoptosis-, and nec...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/32323
The TAT-RasGAP317-326 anti-cancer peptide can kill in a caspase-, apoptosis-, and necroptosis-independent manner
English
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 mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Michel, Sébastien [Université de Lausanne > Department of Physiology]
Kreis, Stephanie mailto [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]
27-Sep-2016
Oncotarget
Impact Journals
7
39
Yes
International
1949-2553
Albany
NY
[en] tumor cell death ; non-apoptotic death ; cell-permeable peptides ; RasGAP
[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.
University of Lausanne
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
Researchers
http://hdl.handle.net/10993/32323
10.18632/oncotarget.11841

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