Transcriptomics

Dataset Information

3

PKCz restrains cancer cell transformation by inhibiting nutrient stress-induced metabolic reprogramming


ABSTRACT: Tumor cells utilize the so-called Warburg effect to allow for rapid proliferation with glucose as the main nutrient. We show here that, although PKCz is critical for that effect, its deficiency promotes the plasticity necessary for nutrient-stressed cancer cells to reprogram their metabolism to utilize glutamine through the serine biosynthetic pathway, empowering them to survive and proliferate in the absence of glucose. We show that PKCz deficiency enhances glutamine utilization and expression of two key enzymes of the pathway, PGHDGH and PSAT1, in cells cultured in the absence of glucose. The loss of PKCz in mice results in enhanced intestinal tumorigenesis and increased levels of these two metabolic enzymes, while patients with low levels of PKCz have a poor prognosis. Taken together, this suggests that PKCz is a critical metabolic tumor suppressor. SW480 cells were infected with lentivirus expressing PKCz RNA interference (shPKCz) and a control lentivirus (shNT). The elimination of endogenous PKCz with shPKCz transfection was >90% efficient. Cells transfected with shNT had unaltered levels of PKCz. To mimic the conditions of nutrient stress to which tumor cells are normally exposed, both cell types were initially seeded in DMEM with 10% FBS, and cultured without subsequent further media changes, which led to nutrient exhaustion over time. Total RNA was harvested from three independent biological replicates for shPKCz and shNT transfected cells.

ORGANISM(S): Homo sapiens  

SUBMITTER: Jing Chen   Alekxey Porollo  Jennifer F Barger  Li Ma  Elias Castilla  Yongzhen Tao  Mario Medvedovic  Adam Richardson  Anita Galvez  Maria T Diaz-Meco  David R Plas  Jorge Moscat 

PROVIDER: E-GEOD-42186 | ArrayExpress | 2013-01-01

SECONDARY ACCESSION(S): GSE42186PRJNA179262

REPOSITORIES: GEO, ArrayExpress

Dataset's files

Source:
Action DRS
E-GEOD-42186.idf.txt Idf
E-GEOD-42186.processed.1.zip Processed
E-GEOD-42186.raw.1.zip Raw
E-GEOD-42186.sdrf.txt Txt
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