Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment

Laura Brohée, Stéphane Demine, Jérome Willems, Thierry Arnould, Alain C. Colige, Christophe F. Deroanne

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)11264-11280
Number of pages17
JournalOncotarget
Volume6
Issue number13
Early online date14 Mar 2015
Publication statusPublished - 10 May 2015

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Sirolimus
Phenotype
Neoplasms
Phosphatidic Acids
Prostatic Neoplasms
lipine
Ribosomal Protein S6
Lipids
Lipogenesis
Diglycerides
Autophagy
Propranolol
Cell Movement
Homeostasis
Phosphorylation
Cell Proliferation
Apoptosis
Breast Neoplasms
Cell Line

Keywords

  • Lipin-1
  • Metabolism
  • Prostate cancer
  • Rapamycin
  • RhoA

Cite this

Brohée, L., Demine, S., Willems, J., Arnould, T., Colige, A. C., & Deroanne, C. F. (2015). Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment. Oncotarget, 6(13), 11264-11280.
Brohée, Laura ; Demine, Stéphane ; Willems, Jérome ; Arnould, Thierry ; Colige, Alain C. ; Deroanne, Christophe F. / Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment. In: Oncotarget. 2015 ; Vol. 6, No. 13. pp. 11264-11280.
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Brohée, L, Demine, S, Willems, J, Arnould, T, Colige, AC & Deroanne, CF 2015, 'Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment', Oncotarget, vol. 6, no. 13, pp. 11264-11280.

Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment. / Brohée, Laura; Demine, Stéphane; Willems, Jérome; Arnould, Thierry; Colige, Alain C.; Deroanne, Christophe F.

In: Oncotarget, Vol. 6, No. 13, 10.05.2015, p. 11264-11280.

Research output: Contribution to journalArticle

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