Glutaminase-1 (GLS1) inhibition limits metastatic progression in osteosarcoma

Cancer & Metabolism
Ling RenAmy LeBlanc

Abstract

Osteosarcoma (OS) is a malignant bone tumor that often develops during the period of rapid growth associated with adolescence. Despite successful primary tumor control accompanied by adjuvant chemotherapy, death from pulmonary metastases occurs in approximately 30% of patients within 5 years. As overall survival in patients remains unchanged over the last 30 years, urgent needs for novel therapeutic strategies exist. Cancer metastasis is characterized by complex molecular events which result from alterations in gene and protein expression/function. Recent studies suggest that metabolic adaptations, or "metabolic reprogramming," may similarly contribute to cancer metastasis. The goal of this study was to specifically interrogate the metabolic vulnerabilities of highly metastatic OS cell lines in a series of in vitro and in vivo experiments, in order to identify a tractable metabolically targeted therapeutic strategy for patients. Nutrient deprivation and drug treatment experiments were performed in MG63.3, 143B, and K7M2 OS cell lines to identify the impact of glutaminase-1 (GLS1) inhibition and metformin treatment on cell proliferation. We functionally validated the impact of drug treatment with extracellular flux analysis, nuc...Continue Reading

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Citations

Jun 25, 2020·Cancers·Victor Ruiz-RodadoMioara Larion
Apr 25, 2020·International Journal of Molecular Sciences·Yunuen Ortiz-PedrazaMarcela Lizano
Jul 19, 2020·Archives of Toxicology·José M MatésJavier Márquez
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Nov 21, 2020·Molecular Cell·Maria I MatiasNaomi Taylor
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Feb 7, 2021·Biomedicines·Wa DuYanbo Fan
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Aug 7, 2021·Metabolites·Jingzhi FanKristaps Klavins
Oct 31, 2021·Journal of Translational Medicine·Taiana Campos LeiteGiuseppe Intini

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Methods Mentioned

BETA
xenograft
inverted microscopy
NMR

Software Mentioned

ImageJ
MetaboAnalyst
ACD Spectrus Processor
R

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