Inhibition of glutamate oxaloacetate transaminase 1 in cancer cell lines results in altered metabolism with increased dependency of glucose

BMC Cancer
Xiaoshan ZhouAnna Karlsson

Abstract

Glutamate oxaloacetate transaminase 1 (GOT1) regulates cellular metabolism through coordinating the utilization of carbohydrates and amino acids to meet nutrient requirements. KRAS mutated cancer cells were recently shown to rely on GOT1 to support long-term cell proliferation. The aim of the present study was to address the role of GOT1 in the metabolic adaption of cancer cells. GOT1-null and knockdown cell lines were established through CRISPR/Cas9 and shRNA techniques. The growth properties, colony formation ability, autophagy and selected gene expression profiles were analysed. Glucose deprivation decreased the viability of the GOT1-null cells and rescue experiments were conducted with selected intermediates. The redox NADH/NAD+ homeostasis as well as lactate secretion were determined. GOT1 expression levels and correlation with survival rates were analysed in selected tumor databases. Inhibition of GOT1 sensitized the cancer cells to glucose deprivation, which was partially counteracted by oxaloacetate and phosphoenol pyruvate, metabolic intermediates downstream of GOT1. Moreover, GOT1-null cells accumulated NADH and displayed a decreased ratio of NADH/NAD+ with nutrient depletion. The relevance of GOT1 as a potential targ...Continue Reading

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Citations

Sep 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ana HipólitoJacinta Serpa
Mar 30, 2020·Cancer Research·Christopher GromischMark W Grinstaff
Aug 20, 2019·Trends in Molecular Medicine·Chunyang JiangZhigang Zhao
Dec 4, 2020·Redox Biology·Anna-Theresa MellisGuenter Schwarz
Nov 3, 2020·Translational Research : the Journal of Laboratory and Clinical Medicine·Antonio Dopico-LópezFrancisco Campos
Dec 29, 2018·Biochemical and Biophysical Research Communications·Juan WangWei Chen
Aug 6, 2021·Computers in Biology and Medicine·Sidharth SaxenaTiratha Raj Singh
Dec 7, 2021·Molecular Metabolism·Naoya MuraoSusumu Seino

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Datasets Mentioned

BETA
GSE

Methods Mentioned

BETA
transfection
PCR
ELISA
RNA-seq

Software Mentioned

GEPIA
CRISPR RNA Configurator
BLOCK

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