Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate
rapamycin treatment
#MMPMID25834103
Brohée L
; Demine S
; Willems J
; Arnould T
; Colige AC
; Deroanne CF
Oncotarget
2015[May]; 6
(13
): 11264-80
PMID25834103
show ga
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.
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