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.
On four occasions during an annual cycle, 5--7 male domestic ducks were injected with two different doses (5 and 20 micrograms) of synthetic luteinizing hormone-releasing hormone (LHRH) to study the possible changes in responsiveness of the pituitary. The luteinizing hormone (LH) and the follicle-stimulating hormone (FSH) were measured in the plasma samples collected after these injections. The induced release of LH changes from one period of the year to another, being minimum in March at the height of the reproductive season. The LHRH injection also induces the release of some FSH but only in limited amounts. The changes in pituitary responsiveness to LHRH are negatively correlated to changes in the circulating LH level (it is high when the plasma LH is low and vice versa). This suggests that the hypothalamic synthesis and release of LHRH must also change during the year.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.