Reference : Relevance of the TRIAP1/p53 axis in colon cancer cell proliferation and adaptation to...

	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Oncology
	To cite this reference:	http://hdl.handle.net/10993/54772

Title :	Relevance of the TRIAP1/p53 axis in colon cancer cell proliferation and adaptation to glutamine deprivation
Language :	English
Author, co-author :	Nedara, Kenza [Université Paris-Saclay, CNRS > Gustave Roussy]
	Reinhardt, Camille [Université Paris-Saclay, CNRS, > Gustave Roussy]
	Lebraud, Emilie [Institut de Radioprotection et de Sûreté Nucléaire Laboratoire de radiobiologie des Expositions Médicales (IRSN), Fontenay-aux-Roses, France]
	Arena, Giuseppe [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience >]
	Gracia, Céline []
	Buard, Valérie []
	Pioche-Durieu, Catherine []
	Castelli, Florence []
	Colsch, Benoit []
	Bénit, Paule []
	Rustin, Pierre []
	Albaud, Benoit []
	Gestraud, Pierre []
	Baulande, Sylvain []
	Servant, Nicolas []
	Deutsch, Eric []
	Verbavatz, Jean-Marc []
	Brenner, Catherine []
	Milliat, Fabien []
	Modjtahedi, Nazanine []
Publication date :	31-Oct-2022
Journal title :	Frontiers in Oncology
Publisher :	Frontiers Media
Volume :	12
Issue/season :	958155
Peer reviewed :	Yes
Audience :	International
ISSN :	2234-943X
e-ISSN :	2234-943X
City :	Lausanne
Country :	Switzerland
Keywords :	[en] p53 ; TRIAP1 ; colon cancer ; glutamine deprivation
Abstract :	[en] Human TRIAP1 (TP53-regulated inhibitor of apoptosis 1; also known as p53CSV for p53-inducible cell survival factor) is the homolog of yeast Mdm35, a well-known chaperone that interacts with the Ups/PRELI family proteins and participates in the intramitochondrial transfer of lipids for the synthesis of cardiolipin (CL) and phosphatidylethanolamine. Although recent reports indicate that TRIAP1 is a prosurvival factor abnormally overexpressed in various types of cancer, knowledge about its molecular and metabolic function in human cells is still elusive. It is therefore critical to understand the metabolic and proliferative advantages that TRIAP1 expression provides to cancer cells. Here, in a colorectal cancer cell model, we report that the expression of TRIAP1 supports cancer cell proliferation and tumorigenesis. Depletion of TRIAP1 perturbed the mitochondrial ultrastructure, without a major impact on CL levels and mitochondrial activity. TRIAP1 depletion caused extramitochondrial perturbations resulting in changes in the endoplasmic reticulum-dependent lipid homeostasis and induction of a p53-mediated stress response. Furthermore, we observed that TRIAP1 depletion conferred a robust p53-mediated resistance to the metabolic stress caused by glutamine deprivation. These findings highlight the importance of TRIAP1 in tumorigenesis and indicate that the loss of TRIAP1 has extramitochondrial consequences that could impact on the metabolic plasticity of cancer cells and their response to conditions of nutrient deprivation.
Target :	Researchers ; Professionals ; Students ; General public
Permalink :	http://hdl.handle.net/10993/54772
DOI :	10.3389/fonc.2022.958155
FnR project :	FnR ; FNR15850547 > Giuseppe Arena > PINK1-DiaPDs > Pink1-related Molecular Mechanisms To Dissect The Connection Between Type 2 Diabetes And Insulin Resistance In Parkinson’S Disease > 01/01/2022 > 31/08/2024 > 2021

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