Article (Scientific journals)
Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment
Brohée, Laura; Demine, Stéphane; Willems, Jérôme et al.
2015In Oncotarget, 6 (13), p. 11264-11280
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Keywords :
prostate cancer; metabolism; rapamycin; RhoA; Lipin-1
Abstract :
[en] Lipogenesis inhibition was reported to induce apoptosis and repress proliferation of cancer cells while barely affecting normal cells. Lipins exhibit dual function as enzymes catalyzing the dephosphorylation of phosphatidic acid to diacylglycerol and as co-transcriptional regulators. Thus, they are able to regulate lipid homeostasis at several nodal points. Here, we show that lipin-1 is up-regulated in several cancer cell lines and overexpressed in 50 % of high grade prostate cancers. The proliferation of prostate and breast cancer cells, but not of non-tumorigenic cells, was repressed upon lipin-1 knock-down. Lipin-1 depletion also decreased cancer cell migration through RhoA activation. Lipin-1 silencing did not significantly affect global lipid synthesis but enhanced the cellular concentration of phosphatidic acid. In parallel, autophagy was induced while AKT and ribosomal protein S6 phosphorylation were repressed. We also observed a compensatory regulation between lipin-1 and lipin-2 and demonstrated that their co-silencing aggravates the phenotype induced by lipin-1 silencing alone. Most interestingly, lipin-1 depletion or lipins inhibition with propranolol sensitized cancer cells to rapamycin. These data indicate that lipin-1 controls main cellular processes involved in cancer progression and that its targeting, alone or in combination with other treatments, could open new avenues in anticancer therapy.
Research center :
Giga-Cancer - ULiège
Disciplines :
Oncology
Biochemistry, biophysics & molecular biology
Author, co-author :
Brohée, Laura ;  Université de Liège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Demine, Stéphane;  Université de Namur > Laboratoire de Biochimie et de Biologie Cellulaire, NARILIS
Willems, Jérôme ;  Université de Liège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Arnould Thierry;  Université de Namur > Laboratoire de Biochimie et de Biologie Cellulaire
Colige, Alain ;  Université de Liège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Deroanne, Christophe ;  Université de Liège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Language :
English
Title :
Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment
Publication date :
10 May 2015
Journal title :
Oncotarget
eISSN :
1949-2553
Publisher :
Impact Journals, Albany, United States - New York
Volume :
6
Issue :
13
Pages :
11264-11280
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Analyse du rôle de la lipin-1 (phosphatidic acid phosphatase-1) dans la progression tumorale et de sa régulation transcriptionnelle et post-traductionnelle par les RhoGTPases
Funders :
Belspo/Prodex
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Available on ORBi :
since 21 May 2015

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