scholarly journals Metabolic reprogramming and epigenetic modifications on the path to cancer

2021 ◽  
Author(s):  
Linchong Sun ◽  
Huafeng Zhang ◽  
Ping Gao
Keyword(s):  
Immune Cells ◽  
Immune Escape ◽  
Epigenetic Modification ◽  
Epigenetic Modifications ◽  
Metabolic Reprogramming ◽  
Epigenetic Alterations ◽  
Metabolic Alterations ◽  
Cancer Hallmarks ◽  
Epigenetic Remodeling ◽  
Spatial Regionalization

AbstractMetabolic rewiring and epigenetic remodeling, which are closely linked and reciprocally regulate each other, are among the well-known cancer hallmarks. Recent evidence suggests that many metabolites serve as substrates or cofactors of chromatin-modifying enzymes as a consequence of the translocation or spatial regionalization of enzymes or metabolites. Various metabolic alterations and epigenetic modifications also reportedly drive immune escape or impede immunosurveillance within certain contexts, playing important roles in tumor progression. In this review, we focus on how metabolic reprogramming of tumor cells and immune cells reshapes epigenetic alterations, in particular the acetylation and methylation of histone proteins and DNA. We also discuss other eminent metabolic modifications such as, succinylation, hydroxybutyrylation, and lactylation, and update the current advances in metabolism- and epigenetic modification-based therapeutic prospects in cancer.

scholarly journals The Complex Interplay between Metabolic Reprogramming and Epigenetic Alterations in Renal Cell Carcinoma

Genes ◽  
2019 ◽  
Vol 10 (4) ◽  
pp. 264 ◽  
Author(s):  
Ana Lameirinhas ◽  
Vera Miranda-Gonçalves ◽  
Rui Henrique ◽  
Carmen Jerónimo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Biological Properties ◽  
Metabolic Reprogramming ◽  
Epigenetic Alterations ◽  
Cancer Hallmarks ◽  
Current Therapies ◽  
Localized Disease ◽  
Common Malignancy

Renal cell carcinoma (RCC) is the most common malignancy affecting the kidney. Current therapies are mostly curative for localized disease, but do not completely preclude recurrence and metastization. Thus, it is imperative to develop new therapeutic strategies based on RCC biological properties. Presently, metabolic reprograming and epigenetic alterations are recognized cancer hallmarks and their interactions are still in its infancy concerning RCC. In this review, we explore RCC biology, highlighting genetic and epigenetic alterations that contribute to metabolic deregulation of tumor cells, including high glycolytic phenotype (Warburg effect). Moreover, we critically discuss available data concerning epigenetic enzymes’ regulation by aberrant metabolite accumulation and their consequences in RCC emergence and progression. Finally, we emphasize the clinical relevance of uncovering novel therapeutic targets based on epigenetic reprograming by metabolic features to improve treatment and survival of RCC patients.

scholarly journals Role of Epigenetic Regulation in Plasticity of Tumor Immune Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunkai Yang ◽  
Yan Wang
Keyword(s):  
Immune Cells ◽  
Noncoding Rna ◽  
Immune Escape ◽  
Genetic Regulation ◽  
Epigenetic Alterations ◽  
Immune Microenvironment ◽  
Post Translational Modifications ◽  
Human Genes ◽  
Tumor Immune Microenvironment

The tumor immune microenvironment (TIME), an immunosuppressive niche, plays a pivotal role in contributing to the development, progression, and immune escape of various types of cancer. Compelling evidence highlights the feasibility of cancer therapy targeting the plasticity of TIME as a strategy to retrain the immunosuppressive immune cells, including innate immune cells and T cells. Epigenetic alterations, such as DNA methylation, histone post-translational modifications, and noncoding RNA-mediated regulation, regulate the expression of many human genes and have been reported to be accurate in the reprogramming of TIME according to vast majority of published results. Recently, mounting evidence has shown that the gut microbiome can also influence the colorectal cancer and even extraintestinal tumors via metabolites or microbiota-derived molecules. A tumor is a kind of heterogeneous disease with specificity in time and space, which is not only dependent on genetic regulation, but also regulated by epigenetics. This review summarizes the reprogramming of immune cells by epigenetic modifications in TIME and surveys the recent progress in epigenetic-based cancer clinical therapeutic approaches. We also discuss the ongoing studies and future areas of research that benefits to cancer eradication.

scholarly journals MicroRNA-Mediated Metabolic Shaping of the Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 127
Author(s):  
Federico Virga ◽  
Lorena Quirico ◽  
Stefania Cucinelli ◽  
Massimiliano Mazzone ◽  
Daniela Taverna ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Immune Cells ◽  
Metabolic Reprogramming ◽  
Stromal Fibroblasts ◽  
Metabolic Alterations ◽  
Cell Functions ◽  
Cancer Management ◽  
Mrna Targets

The metabolism of cancer cells is generally very different from what is found in normal counterparts. However, in a tumor mass, the continuous crosstalk and competition for nutrients and oxygen among different cells lead to metabolic alterations, not only in cancer cells, but also in the different stromal and immune cells of the tumor microenvironment (TME), which are highly relevant for tumor progression. MicroRNAs (miRs) are small non-coding RNAs that silence their mRNA targets post-transcriptionally and are involved in numerous physiological cell functions as well as in the adaptation to stress situations. Importantly, miRs can also be released via extracellular vesicles (EVs) and, consequently, take part in the bidirectional communication between tumor and surrounding cells under stress conditions. Certain miRs are abundantly expressed in stromal and immune cells where they can regulate various metabolic pathways by directly suppressing enzymes or transporters as well as by controlling important regulators (such as transcription factors) of metabolic processes. In this review, we discuss how miRs can induce metabolic reprogramming in stromal (fibroblasts and adipocytes) and immune (macrophages and T cells) cells and, in turn, how the biology of the different cells present in the TME is able to change. Finally, we debate the rebound of miR-dependent metabolic alterations on tumor progression and their implications for cancer management.

scholarly journals Harnessing Metabolic Reprogramming to Improve Cancer Immunotherapy

2021 ◽  
Vol 22 (19) ◽  
pp. 10268
Author(s):  
Liang Yan ◽  
Yanlian Tan ◽  
Guo Chen ◽  
Jun Fan ◽  
Jun Zhang
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Metabolic Pathways ◽  
Immune Escape ◽  
Metabolic Reprogramming ◽  
Immune Microenvironment ◽  
Hallmarks Of Cancer ◽  
Innovative Strategies ◽  
Tumor Immune Microenvironment ◽  
And Function

Immune escape is one of the hallmarks of cancer. While metabolic reprogramming provides survival advantage to tumor cancer cells, accumulating data also suggest such metabolic rewiring directly affects the activation, differentiation and function of immune cells, particularly in the tumor microenvironment. Understanding how metabolic reprogramming affects both tumor and immune cells, as well as their interplay, is therefore critical to better modulate tumor immune microenvironment in the era of cancer immunotherapy. In this review, we discuss alterations in several essential metabolic pathways in both tumor and key immune cells, provide evidence on their dynamic interaction, and propose innovative strategies to improve cancer immunotherapy via the modulation of metabolic pathways.

scholarly journals Metabolic Reprogramming and Immune Evasion in Nasopharyngeal Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Huimei Huang ◽  
Shisheng Li ◽  
Qinglai Tang ◽  
Gangcai Zhu
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cancer Progression ◽  
Immune Cells ◽  
Ph Value ◽  
Treatment Resistance ◽  
Current Treatment ◽  
Nucleotide Metabolism ◽  
Metabolic Reprogramming ◽  
Environmental Pressures ◽  
Cancer Hallmarks

Nasopharyngeal carcinoma (NPC) is a malignant tumor of the nasopharynx mainly characterized by geographic distribution and EBV infection. Metabolic reprogramming, one of the cancer hallmarks, has been frequently reported in NPCs to adapt to internal energy demands and external environmental pressures. Inevitably, the metabolic reprogramming within the tumor cell will lead to a decreased pH value and diverse nutritional supplements in the tumor-infiltrating micro-environment incorporating immune cells, fibroblasts, and endothelial cells. Accumulated evidence indicates that metabolic reprogramming derived from NPC cells may facilitate cancer progression and immunosuppression by cell-cell communications with their surrounding immune cells. This review presents the dysregulated metabolism processes, including glucose, fatty acid, amino acid, nucleotide metabolism, and their mutual interactions in NPC. Moreover, the potential connections between reprogrammed metabolism, tumor immunity, and associated therapy would be discussed in this review. Accordingly, the development of targets on the interactions between metabolic reprogramming and immune cells may provide assistances to overcome the current treatment resistance in NPC patients.

scholarly journals Targeted Glucose or Glutamine Metabolic Therapy Combined With PD-1/PD-L1 Checkpoint Blockade Immunotherapy for the Treatment of Tumors - Mechanisms and Strategies

2021 ◽  
Vol 11 ◽  
Author(s):  
Guofeng Ma ◽  
Chun Li ◽  
Zhilei Zhang ◽  
Ye Liang ◽  
Zhijuan Liang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Immune Escape ◽  
Tumor Therapy ◽  
Checkpoint Blockade ◽  
Metabolic Reprogramming ◽  
Glutamine Metabolism ◽  
Tumor Immune Escape ◽  
New Era ◽  
Cell Expression

Immunotherapy, especially PD-1/PD-L1 checkpoint blockade immunotherapy, has led tumor therapy into a new era. However, the vast majority of patients do not benefit from immunotherapy. One possible reason for this lack of response is that the association between tumors, immune cells and metabolic reprogramming in the tumor microenvironment affect tumor immune escape. Generally, the limited amount of metabolites in the tumor microenvironment leads to nutritional competition between tumors and immune cells. Metabolism regulates tumor cell expression of PD-L1, and the PD-1/PD-L1 immune checkpoint regulates the metabolism of tumor and T cells, which suggests that targeted tumor metabolism may have a synergistic therapeutic effect together with immunotherapy. However, the targeting of different metabolic pathways in different tumors may have different effects on tumor immune escape. Herein, we discuss the influence of glucose metabolism and glutamine metabolism on tumor immune escape and describe the theoretical basis for strategies targeting glucose or glutamine metabolism in combination with PD-1/PD-L1 checkpoint blockade immunotherapy.

Epigenetic modifications in acute lymphoblastic leukemia: From cellular mechanisms to therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Ezzatollah Fathi ◽  
Raheleh Farahzadi ◽  
Soheila Montazersaheb ◽  
Yasin Bagheri
Keyword(s):  
Dna Methylation ◽  
Acute Lymphoblastic Leukemia ◽  
Histone Modification ◽  
Epigenetic Modification ◽  
Lymphoblastic Leukemia ◽  
Underlying Mechanism ◽  
Methylation Pattern ◽  
Epigenetic Alterations ◽  
Cellular Mechanisms ◽  
Novel Treatments

Background:: Epigenetic modification pattern is considered as a characteristic feature in blood malignancies. Modifications in the DNA methylation modulators are recurrent in lymphoma and leukemia, so that, the distinct methylation pattern defines different types of leukemia. Generally, the role of epigenetics is less understood and most investigations are focused on genetic abnormalities and cytogenic studies to develop novel treatments for patients with hematologic disorders. Recently, understanding the underlying mechanism of acute lymphoblastic leukemia (ALL), especially epigenetic altera-tions as a driving force in the development of ALL opens a new era of investigation for developing promising strategy, be-yond available conventional therapy. Objective:: This review will focus on a better understanding of the epigenetic mechanisms in cancer development and pro-gression, with an emphasis on epigenetic alterations in ALL including, DNA methylation, histone modification, and mi-croRNA alterations. Other topics that will be discussed include the use of epigenetic alterations as a promising therapeutic target in order to develop novel well-suited approaches against ALL. Conclusion:: According to the literature review, leukemogenesis of ALL is extensively influenced by epigenetic modifica-tions, particularly DNA hyper-methylation, histone modification, and miRNA alteration.

scholarly journals Genome of a citrus rootstock and global DNA demethylation caused by heterografting

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Yue Huang ◽  
Yuantao Xu ◽  
Xiaolin Jiang ◽  
Huiwen Yu ◽  
Huihui Jia ◽  
...  
Keyword(s):  
Sweet Orange ◽  
Epigenetic Modification ◽  
Epigenetic Modifications ◽  
Genetic Effects ◽  
Dna Demethylation ◽  
Poncirus Trifoliata ◽  
Protein Coding ◽  
Horticultural Crops ◽  
Citrus Rootstock ◽  
Methylome Analysis

AbstractGrafting is an ancient technique used for plant propagation and improvement in horticultural crops for at least 1,500 years. Citrus plants, with a seed-to-seed cycle of 5–15 years, are among the fruit crops that were probably domesticated by grafting. Poncirus trifoliata, a widely used citrus rootstock, can promote early flowering, strengthen stress tolerance, and improve fruit quality via scion–rootstock interactions. Here, we report its genome assembly using PacBio sequencing. We obtained a final genome of 303 Mb with a contig N50 size of 1.17 Mb and annotated 25,680 protein-coding genes. DNA methylome and transcriptome analyses indicated that the strong adaptability of P. trifoliata is likely attributable to its special epigenetic modification and expression pattern of resistance-related genes. Heterografting by using sweet orange as scion and P. trifoliata as rootstock and autografting using sweet orange as both scion and rootstock were performed to investigate the genetic effects of the rootstock. Single-base methylome analysis indicated that P. trifoliata as a rootstock caused DNA demethylation and a reduction in 24-nt small RNAs (sRNAs) in scions compared to the level observed with autografting, implying the involvement of sRNA-mediated graft-transmissible epigenetic modifications in citrus grafting. Taken together, the assembled genome for the citrus rootstock and the analysis of graft-induced epigenetic modifications provide global insights into the genetic effects of rootstock–scion interactions and grafting biology.

Sign in / Sign up

Export Citation Format

Share Document