GLS2 is protumorigenic in breast cancers

Dias, Milton; Adamóski, Douglas; Reis, Larissa Menezes dos; Ascenção, Carolline Fernanda Rodrigues; Oliveira, Krishina Ratna Sousa de; Mafra, Ana Carolina Paschoalini; Bastos, Alliny Cristiny da Silva; Quintero, Melissa; Cassago, Carolina de G.; Ferreira, Igor; Fidelis, Carlos H.V.; Rocco, Silvana A.; Bajgelman, Marcio C.; Stine, Zachary E.; Berindan‐Neagoe, Ioana; Calin, George A.; Ambrósio, André Luís Berteli; Dias, Sandra Martha Gomes

doi:10.1038/s41388-019-1007-z

Cited by 50 publications

(69 citation statements)

References 49 publications

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“…Likewise, GLS2 but not GLS1 could not only inhibit HCC cell migration and invasion in vitro, but also suppress lung metastasis in a mouse model through inhibiting Rac1 activity and mediating p53's function (28). Conversely, Dias et al reported that GLS2 expression was able to increase the EMT markers as well as cancer cell migration and invasion partly through the regulation of ERK and ZEB1 in breast cancer (92), indicating a positive induction of EMT by GLS2. In general, GLS1 shows a positive regulation of EMT process while the functions of GLS2 on EMT are diverse and may be attributed to different tumor types as well as varying degrees of tumor malignancy.…”

Section: Glutaminolysis and Cancer Metastasis: Emt Tumor Immunologymentioning

confidence: 98%

“…On the contrary, Dias et al revealed that GLS2 amplification or overexpression is linked to worse overall, diseasefree and distant metastasis-free survival in breast cancer (92). The increased expression of GLS2 leads to enhanced cell migration, invasion and lung metastasis (92). Consistently, Lukey et al found that the expression of GLS2 supports proliferation and tumorigenesis in luminal subtype breast cancers (78).…”

Section: Opposite Roles Of Gls1 and Gls2 In Tumorigenesismentioning

confidence: 99%

“…Furthermore, Kuo et al demonstrated that expression of GLS2 inversely correlates with poor prognosis and early recurrence in HCC patients (91). On the contrary, Dias et al revealed that GLS2 amplification or overexpression is linked to worse overall, diseasefree and distant metastasis-free survival in breast cancer (92). The increased expression of GLS2 leads to enhanced cell migration, invasion and lung metastasis (92).…”

Section: Opposite Roles Of Gls1 and Gls2 In Tumorigenesismentioning

confidence: 99%

“…Structures of selected inhibitors and the allosteric binding of GLS1 with BPTES and CB-839 are shown in Figure 3 (66). However, less efforts have been made to target GLS2 due to its controversial roles in tumor suppression (26,71,92). Lee et al reported a series of alkyl benzoquinones that preferentially inhibit GLS2 rather than GLS1, which function through the specific binding to an allosteric pocket at the C-terminal end of GLS2 monomer (133).…”

Section: Glutaminase Inhibitor Based Therapeutic Strategymentioning

confidence: 99%

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Targeting Glutaminolysis: New Perspectives to Understand Cancer Development and Novel Strategies for Potential Target Therapies

et al. 2020

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Metabolism rewiring is an important hallmark of cancers. Being one of the most abundant free amino acids in the human blood, glutamine supports bioenergetics and biosynthesis, tumor growth, and the production of antioxidants through glutaminolysis in cancers. In glutamine dependent cancer cells, more than half of the tricarboxylic/critic acid (TCA) metabolites are derived from glutamine. Glutaminolysis controls the process of converting glutamine into TCA cycle metabolites through the regulation of multiple enzymes, among which the glutaminase shows the importance as the very first step in this process. Targeting glutaminolysis via glutaminase inhibition emerges as a promising strategy to disrupt cancer metabolism and tumor progression. Here, we review the regulation of glutaminase and the role of glutaminase in cancer metabolism and metastasis. Furthermore, we highlight the glutaminase inhibitor based metabolic therapy strategy and their potential applications in clinical scenarios.

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Section: Glutaminolysis and Cancer Metastasis: Emt Tumor Immunologymentioning

confidence: 98%

Section: Opposite Roles Of Gls1 and Gls2 In Tumorigenesismentioning

confidence: 99%

Section: Opposite Roles Of Gls1 and Gls2 In Tumorigenesismentioning

confidence: 99%

Section: Glutaminase Inhibitor Based Therapeutic Strategymentioning

confidence: 99%

See 2 more Smart Citations

Targeting Glutaminolysis: New Perspectives to Understand Cancer Development and Novel Strategies for Potential Target Therapies

et al. 2020

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“…TNBC highly depends on glutamine metabolism for progression, which is primarily mediated by glutaminase isoforms (Timmerman et al, 2013). Glutaminase 2 (GLS2) was found to increase mesenchymal markers, invasion, and metastasis (Dias et al, 2020). Conflictingly, another study suggests that the levels of GLS2 are inversely correlated with EMT.…”

Section: Amino Acid Metabolismmentioning

confidence: 99%

Exploring the Metabolic Vulnerabilities of Epithelial–Mesenchymal Transition in Breast Cancer

Sun

Wang

et al. 2020

Front. Cell Dev. Biol.

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Metastasis and drug resistance are the leading causes of death for breast cancer patients. Epithelial-mesenchymal transition (EMT), a transition from polarized epithelial cells to motile mesenchymal cells mediated by a series of activation signals, confers breast tumor cells with enhanced stem cell, invasive, and metastatic properties. Metabolic reprogramming is an emerging hallmark of cancer cells, which have a complex mutual effect with EMT process. Under hypoxic and nutrient-deprived conditions, metabolic rewiring can rapidly provide ATP and sufficient metabolic intermediates for fueling breast cancer metastasis and progression. In this review, we primarily focus on how these altered metabolic phenotypes of breast tumor cells activate the EMT transcription factors and induce the EMT process to further promote metastasis and resistance to therapy. This review is divided to glucose, lipid, and amino acid metabolism to explore for potential metabolic vulnerabilities, which may provide new insights for blocking the EMT process in breast cancer.

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Amino acid metabolic reprogramming in the tumor microenvironment and its implication for cancer therapy

Zhang,

Chen,

Yang

et al. 2024

Journal Cellular Physiology

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Amino acids are essential building blocks for proteins, crucial energy sources for cell survival, and key signaling molecules supporting the resistant growth of tumor cells. In tumor cells, amino acid metabolic reprogramming is characterized by the enhanced uptake of amino acids as well as their aberrant synthesis, breakdown, and transport, leading to immune evasion and malignant progression of tumor cells. This article reviews the altered amino acid metabolism in tumor cells and its impact on tumor microenvironment, and also provides an overview of the current clinical applications of amino acid metabolism. Innovative drugs targeting amino acid metabolism hold great promise for precision and personalized cancer therapy.

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GLS2 is protumorigenic in breast cancers

Cited by 50 publications

References 49 publications

Targeting Glutaminolysis: New Perspectives to Understand Cancer Development and Novel Strategies for Potential Target Therapies

Targeting Glutaminolysis: New Perspectives to Understand Cancer Development and Novel Strategies for Potential Target Therapies

Exploring the Metabolic Vulnerabilities of Epithelial–Mesenchymal Transition in Breast Cancer

Amino acid metabolic reprogramming in the tumor microenvironment and its implication for cancer therapy

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