دورية أكاديمية
Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment
| العنوان: | Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment |
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| المؤلفون: | Brohée, Laura, Demine, Stéphane, Willems, Jérôme, Arnould Thierry, Colige, Alain, Deroanne, Christophe |
| المساهمون: | Giga-Cancer - ULiège |
| المصدر: | Oncotarget, 6 (13), 11264-11280 (2015-05-10) |
| بيانات النشر: | Impact Journals, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | prostate cancer, metabolism, rapamycin, RhoA, Lipin-1, Human health sciences, Oncology, Life sciences, Biochemistry, biophysics & molecular biology, Sciences de la santé humaine, Oncologie, Sciences du vivant, Biochimie, biophysique & biologie moléculaire |
| الوصف: | Lipogenesis inhibition was reported to induce apoptosis and repress proliferationof cancer cells while barely affecting normal cells. Lipins exhibit dual function asenzymes catalyzing the dephosphorylation of phosphatidic acid to diacylglycerol andas co-transcriptional regulators. Thus, they are able to regulate lipid homeostasis atseveral nodal points. Here, we show that lipin-1 is up-regulated in several cancer celllines and overexpressed in 50 % of high grade prostate cancers. The proliferationof prostate and breast cancer cells, but not of non-tumorigenic cells, was repressedupon lipin-1 knock-down. Lipin-1 depletion also decreased cancer cell migrationthrough RhoA activation. Lipin-1 silencing did not significantly affect global lipidsynthesis but enhanced the cellular concentration of phosphatidic acid. In parallel,autophagy was induced while AKT and ribosomal protein S6 phosphorylation wererepressed. We also observed a compensatory regulation between lipin-1 and lipin-2and demonstrated that their co-silencing aggravates the phenotype induced bylipin-1 silencing alone. Most interestingly, lipin-1 depletion or lipins inhibition withpropranolol sensitized cancer cells to rapamycin. These data indicate that lipin-1controls main cellular processes involved in cancer progression and that its targeting,alone or in combination with other treatments, could open new avenues in anticancertherapy. 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 |
| نوع الوثيقة: | journal article http://purl.org/coar/resource_type/c_6501 article peer reviewed |
| اللغة: | English |
| Relation: | http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=3595&path%5B%5D=7297; urn:issn:1949-2553 |
| DOI: | 10.18632/oncotarget.3595 |
| URL الوصول: | https://orbi.uliege.be/handle/2268/181720 |
| حقوق: | open access http://purl.org/coar/access_right/c_abf2 info:eu-repo/semantics/openAccess |
| رقم الأكسشن: | edsorb.181720 |
| قاعدة البيانات: | ORBi |
| DOI: | 10.18632/oncotarget.3595 |
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