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 52 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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Aberrant Energy Metabolism in Tumors and Potential Therapeutic Targets

Fan,

Guo,

Nie

et al. 2024

Genes Chromosomes & Cancer

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Energy metabolic reprogramming is frequently observed during tumor progression as tumor cells necessitate adequate energy production for rapid proliferation. Although current medical research shows promising prospects in studying the characteristics of tumor energy metabolism and developing anti‐tumor drugs targeting energy metabolism, there is a lack of systematic compendiums and comprehensive reviews in this field. The objective of this study is to conduct a systematic review on the characteristics of tumor cells' energy metabolism, with a specific focus on comparing abnormalities between tumor and normal cells, as well as summarizing potential targets for tumor therapy. Additionally, this review also elucidates the aberrant mechanisms underlying four major energy metabolic pathways (glucose, lipid, glutamine, and mitochondria‐dependent) during carcinogenesis and tumor progression. Through the utilization of graphical representations, we have identified anomalies in crucial energy metabolism pathways, encompassing transporter proteins (glucose transporter, CD36, and ASCT2), signaling molecules (Ras, AMPK, and PTEN), as well as transcription factors (Myc, HIF‐1α, CREB‐1, and p53). The key molecules responsible for aberrant energy metabolism in tumors may serve as potential targets for cancer therapy. Therefore, this review provides an overview of the distinct energy‐generating pathways within tumor cells, laying the groundwork for developing innovative strategies for precise cancer treatment.

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GLS2 is protumorigenic in breast cancers

Cited by 52 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

Aberrant Energy Metabolism in Tumors and Potential Therapeutic Targets

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