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

摘要: 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 phosphatidic acid diacylglycerol co-transcriptional regulators. Thus, they are able regulate lipid homeostasis at several nodal points. Here, we show that lipin-1 is up-regulated in cell lines overexpressed 50 % high grade prostate cancers. The breast cells, but not non-tumorigenic repressed upon knock-down. Lipin-1 depletion also decreased migration through RhoA activation. silencing did significantly affect global synthesis enhanced cellular concentration acid. In parallel, autophagy induced AKT ribosomal protein S6 phosphorylation were repressed. We observed a compensatory regulation between lipin-2 demonstrated their co-silencing aggravates phenotype by alone. Most interestingly, or lipins with propranolol sensitized rapamycin. These data indicate controls main processes involved progression its targeting, alone combination other treatments, could open new avenues anticancer therapy.