scholarly journals Glutamine-Derived Aspartate Biosynthesis in Cancer Cells: Role of Mitochondrial Transporters and New Therapeutic Perspectives

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 245
Author(s):  
Ruggiero Gorgoglione ◽  
Valeria Impedovo ◽  
Christopher L. Riley ◽  
Deborah Fratantonio ◽  
Stefano Tiziani ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Cell Metabolism ◽  
Redox Homeostasis ◽  
Nucleotide Biosynthesis ◽  
Specific Tumor ◽  
Mitochondrial Carrier Family ◽  
Cancer Types ◽  
Cancer Cell Metabolism ◽  
Tumor Types

Aspartate has a central role in cancer cell metabolism. Aspartate cytosolic availability is crucial for protein and nucleotide biosynthesis as well as for redox homeostasis. Since tumor cells display poor aspartate uptake from the external environment, most of the cellular pool of aspartate derives from mitochondrial catabolism of glutamine. At least four transporters are involved in this metabolic pathway: the glutamine (SLC1A5_var), the aspartate/glutamate (AGC), the aspartate/phosphate (uncoupling protein 2, UCP2), and the glutamate (GC) carriers, the last three belonging to the mitochondrial carrier family (MCF). The loss of one of these transporters causes a paucity of cytosolic aspartate and an arrest of cell proliferation in many different cancer types. The aim of this review is to clarify why different cancers have varying dependencies on metabolite transporters to support cytosolic glutamine-derived aspartate availability. Dissecting the precise metabolic routes that glutamine undergoes in specific tumor types is of upmost importance as it promises to unveil the best metabolic target for therapeutic intervention.

scholarly journals LKB1/AMPK Pathway and Drug Response in Cancer: A Therapeutic Perspective

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Francesco Ciccarese ◽  
Elisabetta Zulato ◽  
Stefano Indraccolo
Keyword(s):  
Cellular Response ◽  
Cell Metabolism ◽  
Redox Homeostasis ◽  
Suppressor Gene ◽  
Ampk Signaling ◽  
Promising Therapeutic Target ◽  
Liver Kinase B1 ◽  
Nsclc Patients ◽  
Tumor Types

Inactivating mutations of the tumor suppressor gene Liver Kinase B1 (LKB1) are frequently detected in non-small-cell lung cancer (NSCLC) and cervical carcinoma. Moreover, LKB1 expression is epigenetically regulated in several tumor types. LKB1 has an established function in the control of cell metabolism and oxidative stress. Clinical and preclinical studies support a role of LKB1 as a central modifier of cellular response to different stress-inducing drugs, suggesting LKB1 pathway as a highly promising therapeutic target. Loss of LKB1-AMPK signaling confers sensitivity to energy depletion and to redox homeostasis impairment and has been associated with an improved outcome in advanced NSCLC patients treated with chemotherapy. In this review, we provide an overview of the interplay between LKB1 and its downstream targets in cancer and focus on potential therapeutic strategies whose outcome could depend from LKB1.

scholarly journals The Role of Non-Coding RNAs in the Regulation of the Proto-Oncogene MYC in Different Types of Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 921
Author(s):  
Ekaterina Mikhailovna Stasevich ◽  
Matvey Mikhailovich Murashko ◽  
Lyudmila Sergeevna Zinevich ◽  
Denis Eriksonovich Demin ◽  
Anton Markovich Schwartz
Keyword(s):  
Malignant Tumors ◽  
Current Data ◽  
Cellular Processes ◽  
Cell Divisions ◽  
Specific Tumor ◽  
Different Types ◽  
Myc Gene ◽  
Non Coding Rnas ◽  
Tumor Types

Alterations in the expression level of the MYC gene are often found in the cells of various malignant tumors. Overexpressed MYC has been shown to stimulate the main processes of oncogenesis: uncontrolled growth, unlimited cell divisions, avoidance of apoptosis and immune response, changes in cellular metabolism, genomic instability, metastasis, and angiogenesis. Thus, controlling the expression of MYC is considered as an approach for targeted cancer treatment. Since c-Myc is also a crucial regulator of many cellular processes in healthy cells, it is necessary to find ways for selective regulation of MYC expression in tumor cells. Many recent studies have demonstrated that non-coding RNAs play an important role in the regulation of the transcription and translation of this gene and some RNAs directly interact with the c-Myc protein, affecting its stability. In this review, we summarize current data on the regulation of MYC by various non-coding RNAs that can potentially be targeted in specific tumor types.

scholarly journals ROLE OF ACCESS OSTEOTOMY IN HEAD AND NECK LESIONS – A REVIEW

2021 ◽  
pp. 25-30
Author(s):  
BHARATHI K ◽  
MANOJ CHANDRASEKAR ◽  
KAPIL DEV KUMAR S ◽  
BALA JAGANNATH GUPTA B
Keyword(s):  
Head And Neck ◽  
Surgical Resection ◽  
Hand Search ◽  
Surgical Access ◽  
Operative Care ◽  
Specific Tumor ◽  
Surgical Field ◽  
Tumor Types ◽  
Neurovascular Structures

The surgical resection of the head and neck lesions summarizes the principles, classifications, applications, complications, and post-operative care of osteotomy with the standard protocols performed safely. It often poses a great surgical challenge due to the anatomical complexity, difficulty in accessibility, and proximity of vital structures. A multidisciplinary approach is often required in these situations for their better exposure to provide surgical access. Access osteotomy is the choice and type for these head and neck lesions, which are most often based on the anatomic extent of the lesion, vascularity of the lesion, and involvement of neurovascular structures in and around it. The literature search using Medline from the year 1986 to 2019 were performed and textbooks were also collected by hand search from the same period. The role of aggressive surgical resection has not been established for malignant head and neck lesions with the technical feasibility and its efficacy for specific tumor types must be defined by the future studies. Thus, we would like to conclude that access osteotomy allows the surgeon a better view and an access of the surgical field to resect the tumor completely with safer margins, preserving the vital structures, pre-operative functions, and reducing post-operative complications.

Characterization of the role of bezafibrate in cancer cell metabolism and tumorigenesis

Mitochondrion ◽  
2011 ◽  
Vol 11 (4) ◽  
pp. 645-646
Author(s):  
Xiao Wang⁎ ◽  
Carlos T. Moraes
Keyword(s):  
Cancer Cell ◽  
Cell Metabolism ◽  
Cancer Cell Metabolism

scholarly journals TIGAR's promiscuity

2014 ◽  
Vol 458 (3) ◽  
pp. e5-e7 ◽  
Author(s):  
Juan P. Bolaños
Keyword(s):  
Cell Metabolism ◽  
Glucose Consumption ◽  
Pentose Phosphate ◽  
Regulator Protein ◽  
Biochemical Journal ◽  
Cellular Context ◽  
Health And Disease ◽  
Rigorous Study ◽  
Cancer Cell Metabolism

TIGAR [TP53 (tumour protein 53)-induced glycolysis and apoptosis regulator] protein is known for its ability to inhibit glycolysis, shifting glucose consumption towards the pentose phosphate pathway to promote antioxidant protection of cancer cells. According to sequence homology and activity analyses, TIGAR was initially considered to be a fructose-2,6-bisphosphatase; it has thus received much attention in cancer cell metabolism, given its dependence on p53 and the key role of F26BP (fructose 2,6-bisphosphate) at modulating glycolysis and gluconeogenesis. However, in a rigorous study published in this issue of the Biochemical Journal, Gerin and colleagues report that recombinant TIGAR is a 23BPG (2,3-bisphosphoglycerate) phosphatase, although it also dephosphorylates other carboxylic acid-phosphate esters and, weakly, F26BP. As such, inhibition of endogenous TIGAR leads to a dramatic increase in cellular 23BPG, influencing F26BP to a lower extent that depends on the cellular context. These results challenge the currently held notion that TIGAR modulates glycolysis through decreasing F26BP, and opens a yet unrecognized function(s) for TIGAR-mediated 23BPG control of cellular metabolism in health and disease.

scholarly journals Landscape Profiling Analysis of DPP4 in Malignancies: Therapeutic Implication for Tumor Patients With Coronavirus Disease 2019

2021 ◽  
Vol 11 ◽  
Author(s):  
Lingling Shu ◽  
Yang Liu ◽  
Jinyuan Li ◽  
Xiaoping Wu ◽  
Yang Li ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Critical Role ◽  
Therapeutic Effects ◽  
Strong Correlations ◽  
Tumor Patients ◽  
Dipeptidyl Peptidase 4 ◽  
Specific Tumor ◽  
Cancer Types ◽  
Profiling Analysis

Severe coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by pneumonia, lymphopenia, and cytokine storms. Patients with underlying conditions, and especially cancer patients with impaired immunity, are particularly vulnerable to SARS-CoV-2 infection and complications. Although angiotensin converting enzyme II (ACE2) has been identified as a cellular binding receptor for SARS-CoV-2, immunopathological changes in severe cancer patients support the investigation of additional potential receptors such as dipeptidyl peptidase 4 (DPP4), a key immunoregulator. However, a comprehensive profiling analysis of DPP4 in malignancies remains obscure. In this study, using different datasets, we demonstrated the expression of DPP4 in healthy tissues and pan-cancers, showing the risk of different cancer types towards SARS-CoV-2 infection according to DPP4 expression levels. DPP4 expression was positively correlated with infiltrating levels of various immune cells and showed strong correlations with diverse immune marker sets in pan-cancer patients analyzed by Tumor Immune Estimation Resource (TIMER). These findings suggest that increased DPP4 expression in specific cancer patients might account for the high susceptibility to SARS-CoV-2 infection and the induction of cytokine storms. Due to the critical role of DPP4 in immunometabolism, our results indicate that pharmacological inhibition of DPP4 might provide beneficial therapeutic effects for SARS-CoV-2 treatment together with other strategies in specific tumor patients.

scholarly journals Novel Insights into Epigenetic Regulation of IL6 Pathway: In Silico Perspective on Inflammation and Cancer Relationship

2021 ◽  
Vol 22 (18) ◽  
pp. 10172
Author(s):  
Saverio Candido ◽  
Barbara Maria Rita Tomasello ◽  
Alessandro Lavoro ◽  
Luca Falzone ◽  
Giuseppe Gattuso ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Epigenetic Regulation ◽  
Computational Analysis ◽  
The Cancer Genome Atlas ◽  
Post Translational Modifications ◽  
Pathway Gene ◽  
Cancer Genome Atlas ◽  
Cancer Types ◽  
Tumor Types

IL-6 pathway is abnormally hyperactivated in several cancers triggering tumor cell growth and immune system inhibition. Along with genomic mutation, the IL6 pathway gene expression can be affected by DNA methylation, microRNAs, and post-translational modifications. Computational analysis was performed on the Cancer Genome Atlas (TCGA) datasets to explore the role of IL6, IL6R, IL6ST, and IL6R transmembrane isoform expression and their epigenetic regulation in different cancer types. IL6 was significantly modulated in 70% of tumor types, revealing either up- or down-regulation in an approximately equal number of tumors. Furthermore, IL6R and IL6ST were downregulated in more than 10 tumors. Interestingly, the correlation analysis demonstrated that only the IL6R expression was negatively affected by the DNA methylation within the promoter region in most tumors. Meanwhile, only the IL6ST expression was extensively modulated by miRNAs including miR-182-5p, which also directly targeted all three genes. In addition, IL6 upregulated miR-181a-3p, mirR-214-3p, miR-18a-5p, and miR-938, which in turn inhibited the expression of IL6 receptors. Finally, the patients’ survival rate was significantly affected by analyzed targets in some tumors. Our results suggest the relevance of epigenetic regulation of IL6 signaling and pave the way for further studies to validate these findings and to assess the prognostic and therapeutic predictive value of these epigenetic markers on the clinical outcome and survival of cancer patients.

scholarly journals Uncoupling proteins in mitochondria of plants and some microorganisms.

2001 ◽  
Vol 48 (1) ◽  
pp. 145-155 ◽  
Author(s):  
W Jarmuszkiewicz
Keyword(s):  
Higher Plants ◽  
Uncoupling Protein ◽  
Physiological Role ◽  
Acanthamoeba Castellanii ◽  
Uncoupling Proteins ◽  
Protein Activity ◽  
Functional Connection ◽  
Mitochondrial Inner Membrane ◽  
Mitochondrial Carrier Family

Uncoupling proteins, members of the mitochondrial carrier family, are present in mitochondrial inner membrane and mediate free fatty acid-activated, purine-nucleotide-inhibited H+ re-uptake. Since 1995, it has been shown that the uncoupling protein is present in many higher plants and some microorganisms like non-photosynthetic amoeboid protozoon, Acanthamoeba castellanii and non-fermentative yeast Candida parapsilosis. In mitochondria of these organisms, uncoupling protein activity is revealed not only by stimulation of state 4 respiration by free fatty acids accompanied by decrease in membrane potential (these effects being partially released by ATP and GTP) but mainly by lowering ADP/O ratio during state 3 respiration. Plant and microorganism uncoupling proteins are able to divert very efficiently energy from oxidative phosphorylation, competing for deltamicroH+ with ATP synthase. Functional connection and physiological role of uncoupling protein and alternative oxidase, two main energy-dissipating systems in plant-type mitochondria, are discussed.

Cancer Cell Metabolism Featuring Nrf2

2020 ◽  
Vol 17 (3) ◽  
pp. 263-271 ◽  
Author(s):  
Payal Chatterjee ◽  
Mukesh Yadav ◽  
Namrata Chauhan ◽  
Ying Huang ◽  
Yun Luo
Keyword(s):  
Cancer Cells ◽  
Cell Metabolism ◽  
Cellular Metabolism ◽  
Energy Requirements ◽  
Genetic Mutations ◽  
Cellular Protection ◽  
Key Factor ◽  
Cancer Cell Metabolism ◽  
Cancerous Cells

Although the major role of Nrf2 has long been established as a transcription factor for providing cellular protection against oxidative stress, multiple pieces of research and reviews now claim exactly the opposite. The dilemma - “to activate or inhibit” the protein requires an immediate answer, which evidently links cellular metabolism to the causes and purpose of cancer. Profusely growing cancerous cells have prolific energy requirements, which can only be fulfilled by modulating cellular metabolism. This review highlights the cause and effect of Nrf2 modulation in cancer that in turn channelize cellular metabolism, thereby fulfilling the energy requirements of cancer cells. The present work also highlights the purpose of genetic mutations in Nrf2, in relation to cellular metabolism in cancer cells, thus pointing out a newer approach where parallel mutations may be the key factor to decide whether to activate or inhibit Nrf2.

scholarly journals Inhibition of CDK4/6 as Therapeutic Approach for Ovarian Cancer Patients: Current Evidences and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3035
Author(s):  
Alessandra Dall'Acqua ◽  
Michele Bartoletti ◽  
Nastaran Masoudi-Khoram ◽  
Roberto Sorio ◽  
Fabio Puglisi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Therapeutic Targets ◽  
Metastatic Breast ◽  
Molecular Alterations ◽  
Estrogen Receptor Positive ◽  
Cancer Types ◽  
Almost All ◽  
Tumor Types

Alterations in components of the cell-cycle machinery are present in essentially all tumor types. In particular, molecular alterations resulting in dysregulation of the G1 to S phase transition have been observed in almost all human tumors, including ovarian cancer. These alterations have been identified as potential therapeutic targets in several cancer types, thereby stimulating the development of small molecule inhibitors of the cyclin dependent kinases. Among these, CDK4 and CDK6 inhibitors confirmed in clinical trials that CDKs might indeed represent valid therapeutic targets in, at least some, types of cancer. CDK4 and CDK6 inhibitors are now used in clinic for the treatment of patients with estrogen receptor positive metastatic breast cancer and their clinical use is being tested in many other cancer types, alone or in combination with other agents. Here, we review the role of CDK4 and CDK6 complexes in ovarian cancer and propose the possible use of their inhibitors in the treatment of ovarian cancer patients with different types and stages of disease.

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