mTOR Regulation of Metabolism in Hematologic Malignancies

Mirabilii, Simone; Ricciardi, Maria Rosaria; Tafuri, Agostino

doi:10.3390/cells9020404

Cited by 14 publications

(12 citation statements)

References 129 publications

(150 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously found that DNA hypomethylation due to DNMT3A mutation could lead to the mechanistic target of rapamycin (mTOR) activation [15]. Inhibition of mTOR with rapamycin could reduce glucose uptake in AML cells, which fluctuates among different AML cell lines due to different intracellular signaling [33]. The mTOR complexes play essential roles in mammals in the aspects of lipid biosynthesis, adipogenesis and lipid consumption [34].…”

Section: Discussionmentioning

confidence: 99%

Endothelial lipase promotes acute myeloid leukemia progression through metabolic reprogramming

Shang¹,

Yang²,

Shi³

et al. 2022

neo

View full text Add to dashboard Cite

Metabolic reprogramming occurs in the clonal evolution of acute myeloid leukemia (AML), which contributes to cell survival under metabolic stress and the development of drug resistance.Leukemic cells exhibit various metabolic profiles, which involve multiple metabolic pathways due to the heterogeneity of AML. However, studies on metabolic targets for AML treatment are mostly focused on glycolysis at present. In this work, we established conditional knock-in AML mouse models harboring Dnmt3aR878H/WT, NrasG12D/WT, and both of the mutations, respectively. Transcriptomic analysis of Gr1+ cells from bone marrow was performed afterward to screen interested metabolic pathways and target genes. Candidate genes were studied using the CRISPR/Cas9 technique, quantitative real-time RT-PCR, and flow cytometric analyses. We revealed that multiple metabolic pathways were affected in AML mice, including lipid metabolism.Endothelial lipase (LIPG) was obviously upregulated in leukemic cells from AML mice with Dnmt3a mutation. We performed knockout of LIPG in OCI-AML3 cells carrying DNMT3A R882C mutation by using the CRISPR/Cas9 technique. Depletion of LIPG led to proliferation inhibition, apoptosis, damage of antioxidant capacity, and myeloid differentiation in OCI-AML3 cells. LIPG might serve as a potential metabolic target for the treatment of AML with abnormal lipid metabolism.

show abstract

Section: Discussionmentioning

confidence: 99%

Endothelial lipase promotes acute myeloid leukemia progression through metabolic reprogramming

Shang¹,

Yang²,

Shi³

et al. 2022

neo

View full text Add to dashboard Cite

show abstract

“…Because its C-terminal is homologous with the catalytic domain of phosphatidylinositol kinase (PI3K), it belongs to the PI3K-related protein kinase family. In hematological malignancies, over-activated mTOR is associated with other metabolic regulators, such as AMPK and HIF-1α, in combination with microenvironment stimulation, which can regulate the activities of glycolytic enzymes in a directly or indirectly way to obtain a new glycolytic phenotype [ 31 ]. However, recent studies have found that mTOR signaling pathway may be closely related to the methylation of m6A in regulating tumor metabolism.…”

Section: The M6a and Metabolic Signaling Pathwaysmentioning

confidence: 99%

The role of m6A RNA methylation in cancer metabolism

2022

View full text Add to dashboard Cite

Metabolic reprogramming is one of the main characteristics of malignant tumors, which is due to the flexible changes of cell metabolism that can meet the needs of cell growth and maintain the homeostasis of tissue environments. Cancer cells can obtain metabolic adaptation through a variety of endogenous and exogenous signaling pathways, which can not only promote the growth of malignant cancer cells, but also start the transformation process of cells to adapt to tumor microenvironment. Studies show that m6A RNA methylation is widely involved in the metabolic recombination of tumor cells. In eukaryotes, m6A methylation is the most abundant modification in mRNA, which is involved in almost all the RNA cycle stages, including regulation the transcription, maturation, translation, degradation and stability of mRNA. M6A RNA methylation can be involved in the regulation of physiological and pathological processes, including cancer. In this review, we discuss the role of m6A RNA methylation modification plays in tumor metabolism-related molecules and pathways, aiming to show the importance of targeting m6A in regulating tumor metabolism.

show abstract

“…The mechanistic target of rapamycin (mTOR) signaling, usually activated in tumors, plays a significant role in tumor metabolism modulating gene transcription and protein synthesis to influence cellular activities. 114,115 The mTOR, expert in integrating environmental stimulations into cellular responses, is an evolutionary conserved serine/threonine kinase. 116 Additionally, mTOR could be classified into two complexes, including mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).…”

Section: Mtor Signalingmentioning

confidence: 99%

<p>Emerging Roles and Therapeutic Interventions of Aerobic Glycolysis in Glioma</p>

Han¹,

Shi²,

Cao³

et al. 2020

OTT

View full text Add to dashboard Cite

Glioma is the most common type of intracranial malignant tumor, with a great recurrence rate due to its infiltrative growth, treatment resistance, intra-and intertumoral genetic heterogeneity. Recently, accumulating studies have illustrated that activated aerobic glycolysis participated in various cellular and clinical activities of glioma, thus influencing the efficacy of radiotherapy and chemotherapy. However, the glycolytic process is too complicated and ambiguous to serve as a novel therapy for glioma. In this review, we generalized the implication of key enzymes, glucose transporters (GLUTs), signalings and transcription factors in the glycolytic process of glioma. In addition, we summarized therapeutic interventions via the above aspects and discussed promising clinical applications for glioma.

show abstract

mTOR Regulation of Metabolism in Hematologic Malignancies

Cited by 14 publications

References 129 publications

Endothelial lipase promotes acute myeloid leukemia progression through metabolic reprogramming

Endothelial lipase promotes acute myeloid leukemia progression through metabolic reprogramming

The role of m6A RNA methylation in cancer metabolism

<p>Emerging Roles and Therapeutic Interventions of Aerobic Glycolysis in Glioma</p>

Contact Info

Product

Resources

About