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A Late G1 Lipid Checkpoint That Is Dysregulated in Clear Cell Renal Carcinoma Cells.

The Journal of biological chemistry (2016-12-14)
Deven Patel, Darin Salloum, Mahesh Saqcena, Amrita Chatterjee, Victoria Mroz, Michael Ohh, David A Foster
ABSTRACT

Lipids are important nutrients that proliferating cells require to maintain energy homeostasis as well as to build plasma membranes for newly synthesized cells. Previously, we identified nutrient-sensing checkpoints that exist in the latter part of the G1 phase of the cell cycle that are dependent upon essential amino acids, Gln, and finally, a checkpoint mediated by mammalian target of rapamycin (mTOR), which integrates signals from both nutrients and growth factors. In this study, we have identified and temporally mapped a lipid-mediated G1 checkpoint. This checkpoint is located after the Gln checkpoint and before the mTOR-mediated cell cycle checkpoint. Intriguingly, clear cell renal cell carcinoma cells (ccRCC) have a dysregulated lipid-mediated checkpoint due in part to defective phosphatase and tensin homologue (PTEN). When deprived of lipids, instead of arresting in G1, these cells continue to cycle and utilize lipid droplets as a source of lipids. Lipid droplets have been known to maintain endoplasmic reticulum homeostasis and prevent cytotoxic endoplasmic reticulum stress in ccRCC. Dysregulation of the lipid-mediated checkpoint forces these cells to utilize lipid droplets, which could potentially lead to therapeutic opportunities that exploit this property of ccRCC.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
RPMI-1640 Medium, With L-glutamine and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Dulbecco′s Modified Eagle′s Medium - high glucose, With 4500 mg/L glucose, L-glutamine, sodium pyruvate, and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Lipid (Oil Red O) Staining Kit, Sufficient for 2 96-well plates
Sigma-Aldrich
Fetal Bovine Serum, USA origin, Heat Inactivated, sterile-filtered, suitable for cell culture, suitable for insect cell culture, suitable for hybridoma
Sigma-Aldrich
Dulbecco′s Modified Eagle′s Medium - low glucose, With 1000 mg/L glucose, and sodium bicarbonate, without L-glutamine, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Fetal Bovine Serum, USA origin, Dialyzed by ultrafiltration against 0.15 M NaCl, sterile-filtered, suitable for cell culture
SAFC
Dulbecco′s Modified Eagle′s Medium - low glucose, liquid, sterile-filtered, suitable for cell culture, designed for isotope labeling in cell culture applications