Glutamine metabolism in tumor metastasis: Genes, mechanisms and the therapeutic targets

Zhong, Xugang; He, Zeju; Yin, Li; Fan, Yong; Tong, Yu; Kang, Yao; Bi, Qing

doi:10.1016/j.heliyon.2023.e20656

Cited by 7 publications

(3 citation statements)

References 123 publications

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“…Metastasis is associated with advanced PCa staging and poor prognosis [ 33 ]. Increased Gln utilisation of PCa cells has been linked to increased metastatic potential [ 34 , 35 ]. Moreover, inhibition of Gln uptake decreased tumour growth and metastasis [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, inhibition of Gln uptake decreased tumour growth and metastasis [ 36 ]. Glutaminolysis inhibition has generally reduced disease recurrence risk and metastases in several tumour entities [ 35 , 37 ]. Therefore, the influence of Gln on the clonogenic potential, migration, invasion, and adhesion was investigated within this study.…”

Section: Discussionmentioning

confidence: 99%

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Targeting the glutamine metabolism to suppress cell proliferation in mesenchymal docetaxel-resistant prostate cancer

Beier,

Ebersbach,

Siciliano

et al. 2024

Oncogene

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Docetaxel (DX) serves as a palliative treatment option for metastatic prostate cancer (PCa). Despite initial remission, acquired DX resistance is inevitable. The mechanisms behind DX resistance have not yet been deciphered, but a mesenchymal phenotype is associated with DX resistance. Mesenchymal phenotypes have been linked to metabolic rewiring, obtaining most ATP production by oxidative phosphorylation (OXPHOS) powered substantially by glutamine (Gln). Likewise, Gln is known to play an essential role in modulating bioenergetic, redox homeostasis and autophagy. Herein, investigations of Gln deprivation on DX-sensitive and -resistant (DR) PCa cells revealed that the DR cell sub-lines were susceptible to Gln deprivation. Mechanistically, Gln deprivation reduced OXPHOS and ATP levels, causing a disturbance in cell cycle progression. Genetic and chemical inhibition of the Gln-metabolism key protein GLS1 could validate the Gln deprivation results, thereby representing a valid therapeutic target. Moreover, immunohistological investigation of GLS1 revealed a high-expressing GLS1 subgroup post-docetaxel failure, exhibiting low overall survival. This subgroup presents an intriguing opportunity for targeted therapy focusing on glutamine metabolism. Thus, these findings highlight a possible clinical rationale for the chemical inhibition of GLS1 as a therapeutic strategy to target mesenchymal DR PCa cells, thereby delaying accelerated tumour progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Targeting the glutamine metabolism to suppress cell proliferation in mesenchymal docetaxel-resistant prostate cancer

Beier,

Ebersbach,

Siciliano

et al. 2024

Oncogene

View full text Add to dashboard Cite

show abstract

“…Despite being an essential amino acid, glutamine is abundant in the human body, particularly in the blood and muscles, constituting more than 20% of the free amino acid pool in the blood [ 138 ]. In the context of tumor cells converting glucose to lactic acid, glutamine plays a crucial role in supporting mitochondrial oxidative metabolism, sustaining energy metabolism, and inducing intracellular homeostasis.…”

Section: Altered Metabolism In Bone Metastasismentioning

confidence: 99%

Bridging the Gap in Understanding Bone Metastasis: A Multifaceted Perspective

Elaasser,

Arakil,

Mohammad

2024

IJMS

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The treatment of patients with advanced cancer poses clinical problems due to the complications that arise as the disease progresses. Bone metastases are a common problem that cancer patients may face, and currently, there are no effective drugs to treat these individuals. Prostate, breast, and lung cancers often spread to the bone, causing significant and disabling health conditions. The bone is a highly active and dynamic tissue and is considered a favorable environment for the growth of cancer. The role of osteoblasts and osteoclasts in the process of bone remodeling and the way in which their interactions change during the progression of metastasis is critical to understanding the pathophysiology of this disease. These interactions create a self-perpetuating loop that stimulates the growth of metastatic cells in the bone. The metabolic reprogramming of both cancer cells and cells in the bone microenvironment has serious implications for the development and progression of metastasis. Insight into the process of bone remodeling and the systemic elements that regulate this process, as well as the cellular changes that occur during the progression of bone metastases, is critical to the discovery of a cure for this disease. It is crucial to explore different therapeutic options that focus specifically on malignancy in the bone microenvironment in order to effectively treat this disease. This review will focus on the bone remodeling process and the effects of metabolic disorders as well as systemic factors like hormones and cytokines on the development of bone metastases. We will also examine the various therapeutic alternatives available today and the upcoming advances in novel treatments.

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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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Glutamine metabolism in tumor metastasis: Genes, mechanisms and the therapeutic targets

Cited by 7 publications

References 123 publications

Targeting the glutamine metabolism to suppress cell proliferation in mesenchymal docetaxel-resistant prostate cancer

Targeting the glutamine metabolism to suppress cell proliferation in mesenchymal docetaxel-resistant prostate cancer

Bridging the Gap in Understanding Bone Metastasis: A Multifaceted Perspective

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

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