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Series GSE66556 Query DataSets for GSE66556
Status Public on Oct 15, 2015
Title Mitochondrial phosphoenolpyruvate carboxykinase (PCK2) regulates metabolic adaptation and glucose-independent tumor cell growth
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Cancer cells must adapt metabolically to survive and proliferate when nutrients are limiting. Here we used combined transcriptional-metabolomic network analysis to identify metabolic pathways that support glucose-independent tumor cell growth. We found that glucose deprivation stimulated the re-wiring of the tricarboxylic acid (TCA) cycle and co-opting early steps of gluconeogenesis to promote cell proliferation under low glucose. Glucose limitation promoted the production of phosphoenolpyruvate (PEP) from glutamine, which was used to fuel biosynthetic pathways normally sustained by glucose, including serine and purine biosynthesis. Mitochondrial PEP-carboxykinase (PCK2) was required for this glutamine-dependent metabolic reprogramming. PCK2 expression was dependent on the hypoxia-inducible factors (HIFs), and required to maintain tumor cell proliferation under limiting glucose availability. Elevated PCK2 expression is observed in several human tumor types, and enriched in tumor tissue from non-small cell lung cancer (NSCLC) patients. Our results define a novel role for PCK2 in cancer cell metabolic reprogramming that promotes glucose-independent cell growth and metabolic stress resistance in human tumors.
Overall design A549 cell line was obtained from ATCC (Manassas, VA, USA). A549 cells were cultured in the presence (25 mM) or absence of glucose for 48 hours prior to RNA extraction.
Contributor(s) Sergushichev AA, Artyomov MN
Citation(s) 26474064
Submission date Mar 05, 2015
Last update date May 15, 2019
Contact name Maxim N. Artyomov
Organization name Washington University in St.Louis
Department Immunology&Pathology
Street address 660 S. Euclid Avenue, Campus Box 8118
City St.Louis
State/province MO
ZIP/Postal code 63110
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (6)
GSM1624969 A549_glu_pos_rep1
GSM1624970 A549_glu_pos_rep2
GSM1624971 A549_glu_pos_rep3
BioProject PRJNA277316
SRA SRP055863

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Supplementary file Size Download File type/resource
GSE66556_counts.tsv.gz 182.2 Kb (ftp)(http) TSV
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