scholarly journals Emergence of MicroRNAs as Key Players in Cancer Cell Metabolism

2019 ◽  
Vol 65 (9) ◽  
pp. 1090-1101 ◽  
Author(s):  
Sugarniya Subramaniam ◽  
Varinder Jeet ◽  
Judith A Clements ◽  
Jennifer H Gunter ◽  
Jyotsna Batra
Keyword(s):  
Fatty Acid ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Tca Cycle ◽  
Metabolic Reprogramming ◽  
Metabolic Adaptation ◽  
Novel Therapeutic

AbstractBACKGROUNDMetabolic reprogramming is a hallmark of cancer. MicroRNAs (miRNAs) have been found to regulate cancer metabolism by regulating genes involved in metabolic pathways. Understanding this layer of complexity could lead to the development of novel therapeutic approaches.CONTENTmiRNAs are noncoding RNAs that have been implicated as master regulators of gene expression. Studies have revealed the role of miRNAs in the metabolic reprogramming of tumor cells, with several miRNAs both positively and negatively regulating multiple metabolic genes. The tricarboxylic acid (TCA) cycle, aerobic glycolysis, de novo fatty acid synthesis, and altered autophagy allow tumor cells to survive under adverse conditions. In addition, major signaling molecules, hypoxia-inducible factor, phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin/phosphatase and tensin homolog, and insulin signaling pathways facilitate metabolic adaptation in tumor cells and are all regulated by miRNAs. Accumulating evidence suggests that miRNA mimics or inhibitors could be used to modulate the activity of miRNAs that drive tumor progression via altering their metabolism. Currently, several clinical trials investigating the role of miRNA-based therapy for cancer have been launched that may lead to novel therapeutic interventions in the future.SUMMARYIn this review, we summarize cancer-related metabolic pathways, including glycolysis, TCA cycle, pentose phosphate pathway, fatty acid metabolism, amino acid metabolism, and other metabolism-related oncogenic signaling pathways, and their regulation by miRNAs that are known to lead to tumorigenesis. Further, we discuss the current state of miRNA therapeutics in the clinic and their future potential.

scholarly journals MYC Expression and Metabolic Redox Changes in Cancer Cells: A Synergy Able to Induce Chemoresistance

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Barbara Marengo ◽  
Ombretta Garbarino ◽  
Andrea Speciale ◽  
Lorenzo Monteleone ◽  
Nicola Traverso ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Tumor Suppressors ◽  
Molecular Targets ◽  
Therapy Resistance ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Metabolic Adaptation ◽  
Multiple Factors ◽  
Glutamine Transporters

Chemoresistance is due to multiple factors including the induction of a metabolic adaptation of tumor cells. In fact, in these cells, stress conditions induced by therapies stimulate a metabolic reprogramming which involves the strengthening of various pathways such as glycolysis, glutaminolysis and the pentose phosphate pathway. This metabolic reprogramming is the result of a complex network of mechanisms that, through the activation of oncogenes (i.e., MYC, HIF1, and PI3K) or the downregulation of tumor suppressors (i.e., TP53), induces an increased expression of glucose and/or glutamine transporters and of glycolytic enzymes. Therefore, in order to overcome chemoresistance, it is necessary to develop combined therapies which are able to selectively and simultaneously act on the multiple molecular targets responsible for this adaptation. This review is focused on highlighting the role of MYC in modulating the epigenetic redox changes which are crucial in the acquisition of therapy resistance.

scholarly journals Targets (Metabolic Mediators) of Therapeutic Importance in Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 21 (22) ◽  
pp. 8502
Author(s):  
Vikrant Rai ◽  
Swati Agrawal
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Cells ◽  
Therapeutic Potential ◽  
Therapeutic Targets ◽  
The United States ◽  
Metabolic Reprogramming ◽  
Ductal Adenocarcinoma ◽  
Advanced Stages ◽  
Novel Therapeutic

Pancreatic ductal adenocarcinoma (PDAC), an extremely aggressive invasive cancer, is the fourth most common cause of cancer-related death in the United States. The higher mortality in PDAC is often attributed to the inability to detect it until it has reached advanced stages. The major challenge in tackling PDAC is due to its elusive pathology, minimal effectiveness, and resistance to existing therapeutics. The aggressiveness of PDAC is due to the capacity of tumor cells to alter their metabolism, utilize the diverse available fuel sources to adapt and grow in a hypoxic and harsh environment. Therapeutic resistance is due to the presence of thick stroma with poor angiogenesis, thus making drug delivery to tumor cells difficult. Investigating the metabolic mediators and enzymes involved in metabolic reprogramming may lead to the identification of novel therapeutic targets. The metabolic mediators of glucose, glutamine, lipids, nucleotides, amino acids and mitochondrial metabolism have emerged as novel therapeutic targets. Additionally, the role of autophagy, macropinocytosis, lysosomal transport, recycling, amino acid transport, lipid transport, and the role of reactive oxygen species has also been discussed. The role of various pro-inflammatory cytokines and immune cells in the pathogenesis of PDAC and the metabolites involved in the signaling pathways as therapeutic targets have been previously discussed. This review focuses on the therapeutic potential of metabolic mediators in PDAC along with stemness due to metabolic alterations and their therapeutic importance.

scholarly journals Targeting IDH1 as a pro-senescent therapy in high-grade serous ovarian cancer

2018 ◽  
Author(s):  
Erika S. Dahl ◽  
Raquel Buj ◽  
Kelly E. Leon ◽  
Jordan M. Newell ◽  
Benjamin G. Bitler ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Aerobic Glycolysis ◽  
Gynecological Cancer ◽  
Significant Proportion ◽  
Tca Cycle ◽  
Metabolic Reprogramming ◽  
Serous Carcinoma ◽  
Metabolic Adaptation ◽  
High Grade ◽  
Novel Therapeutic

AbstractEpithelial ovarian cancer (EOC) is the deadliest gynecological cancer. High-grade serous carcinoma (HGSC) is the most frequently diagnosed and lethal histosubtype of EOC. A significant proportion of HGSC patients relapse with chemoresistant disease. Therefore, there is an urgent need for novel therapeutic strategies for HGSC. Metabolic reprogramming is a hallmark of cancer cells, and targeting metabolism for cancer therapy may be beneficial. Here we found that in comparison to normal fallopian tube epithelial cells, HGSC cells preferentially utilize glucose in the TCA cycle and not for aerobic glycolysis. This correlated with universally increased TCA cycle enzyme expression in HGSC cells under adherent conditions. To further differentiate the necessity of TCA cycle enzymes in ovarian cancer progression, we found that only wildtype isocitrate dehydrogenase I (IDH1) is both significantly increased in HGSC cells in spheroid conditions and is associated with reduced progression-free survival. IDH1 protein expression is also increased in primary HGSC patient tumors. Pharmacological inhibition or knockdown of IDH1 decreased proliferation of multiple HGSC cell lines by inducing senescence. Mechanistically, suppression of IDH1 increased the repressive histone mark H3K9me2 at proliferation promoting gene loci (PCNA and MCM3), which led to decreased mRNA expression. Altogether, these data suggest that increased IDH1 activity is an important metabolic adaptation in HGSC and that targeting wildtype IDH1 in HGSC alters the repressive histone epigenetic landscape to induce senescence. Therefore, inhibition of IDH1 may act as a novel therapeutic approach to alter both the metabolism and epigenetics of HGSC as a pro-senescent therapy.

scholarly journals The Role of Tumour Metabolism in Cisplatin Resistance

2021 ◽  
Vol 8 ◽  
Author(s):  
Lude Wang ◽  
Xiaoya Zhao ◽  
Jianfei Fu ◽  
Wenxia Xu ◽  
Jianlie Yuan
Keyword(s):  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Cisplatin Resistance ◽  
Tumour Progression ◽  
Tumour Cells ◽  
Metabolic Reprogramming ◽  
Antitumour Effect ◽  
Damage Repair

Cisplatin is a chemotherapy drug commonly used in cancer treatment. Tumour cells are more sensitive to cisplatin than normal cells. Cisplatin exerts an antitumour effect by interfering with DNA replication and transcription processes. However, the drug-resistance properties of tumour cells often cause loss of cisplatin efficacy and failure of chemotherapy, leading to tumour progression. Owing to the large amounts of energy and compounds required by tumour cells, metabolic reprogramming plays an important part in the occurrence and development of tumours. The interplay between DNA damage repair and metabolism also has an effect on cisplatin resistance; the molecular changes to glucose metabolism, amino acid metabolism, lipid metabolism, and other metabolic pathways affect the cisplatin resistance of tumour cells. Here, we review the mechanism of action of cisplatin, the mechanism of resistance to cisplatin, the role of metabolic remodelling in tumorigenesis and development, and the effects of common metabolic pathways on cisplatin resistance.

scholarly journals The Immunometabolic Roles of Various Fatty Acids in Macrophages and Lymphocytes

2021 ◽  
Vol 22 (16) ◽  
pp. 8460
Author(s):  
Jose Cesar Rosa Neto ◽  
Philip C. Calder ◽  
Rui Curi ◽  
Philip Newsholme ◽  
Jaswinder K. Sethi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Inflammatory Response ◽  
Acid Metabolism ◽  
Mechanisms Of Action ◽  
Metabolic Reprogramming ◽  
Metabolic Plasticity ◽  
Exciting Area

Macrophages and lymphocytes demonstrate metabolic plasticity, which is dependent partly on their state of activation and partly on the availability of various energy yielding and biosynthetic substrates (fatty acids, glucose, and amino acids). These substrates are essential to fuel-based metabolic reprogramming that supports optimal immune function, including the inflammatory response. In this review, we will focus on metabolism in macrophages and lymphocytes and discuss the role of fatty acids in governing the phenotype, activation, and functional status of these important cells. We summarize the current understanding of the pathways of fatty acid metabolism and related mechanisms of action and also explore possible new perspectives in this exciting area of research.

Current Study of RhoA and Associated Signaling Pathways in Gastric Cancer

2020 ◽  
Vol 15 (7) ◽  
pp. 607-613 ◽  
Author(s):  
Haiping Liu ◽  
Yiqian Liu ◽  
Xiaochuan Zhang ◽  
Xiaodong Wang
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Actin Polymerization ◽  
Cell Transformation ◽  
Cell Movement ◽  
Invasion And Metastasis ◽  
Common Cancer

Gastric cancer (GC) is the fourth-most common cancer in the world, with an estimated 1.034 million new cases in 2015, and the third-highest cause of cancer deaths, estimated at 785,558, in 2014. Early diagnosis and treatment greatly affect the survival rate in patients with GC: the 5‐year survival rate of early GC reaches 90%‐95%, while the mortality rate significantly increases if GC develops to the late stage. Recently, studies for the role of RhoA in the diseases have become a hot topic, especially in the development of tumors. A study found that RhoA can regulate actin polymerization, cell adhesion, motor-myosin, cell transformation, and the ability to participate in the activities of cell movement, proliferation, migration, which are closely related to the invasion and metastasis of tumor cells. However, the specific role of RhoA in tumor cells remains to be studied. Therefore, our current study aimed to briefly review the role of RhoA in GC, especially for its associated signaling pathways involved in the GC progression.

scholarly journals Role of dendritic cell metabolic reprogramming in tumor immune evasion

2020 ◽  
Vol 32 (7) ◽  
pp. 485-491 ◽  
Author(s):  
Michael P Plebanek ◽  
Michael Sturdivant ◽  
Nicholas C DeVito ◽  
Brent A Hanks
Keyword(s):  
Dendritic Cell ◽  
Metabolic Pathways ◽  
Checkpoint Inhibitor ◽  
Therapeutic Strategies ◽  
Metabolic Reprogramming ◽  
Combination Immunotherapy ◽  
Tumor Immune Evasion ◽  
Effector T Cell ◽  
Cell Responses

Abstract The dendritic cell (DC) is recognized as a vital mediator of anti-tumor immunity. More recent studies have also demonstrated the important role of DCs in the generation of effective responses to checkpoint inhibitor immunotherapy. Metabolic programming of DCs dictates their functionality and can determine which DCs become immunostimulatory versus those that develop a tolerized phenotype capable of actively suppressing effector T-cell responses to cancers. As a result, there is great interest in understanding what mechanisms have evolved in cancers to alter these metabolic pathways, thereby allowing for their continued progression and metastasis. The therapeutic strategies developed to reverse these processes of DC tolerization in the tumor microenvironment represent promising candidates for future testing in combination immunotherapy clinical trials.

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