Abstract：
:Data obtained from cutting-edge research have shown that deregulated epigenetic marks are critical hallmarks of cancer. Rapidly emerging scientific evidence has helped in developing a proper understanding of the mechanisms leading to control of cellular functions, from changes in chromatin accessibility, transcription and translation, and in post-translational modifications. Firstly, mechanisms of DNA methylation and demethylation are introduced, as well as modifications of DNA and RNA, with particular focus on N6-methyladenosine (m6A), discussing the effects of these modifications in normal cells and in malignancies. Then, chromatin modifying proteins and remodelling complexes are discussed. Many enzymes and accessory proteins in these complexes have been found mutated or have undergone differential splicing, leading to defective protein complexes. Epigenetic mechanisms acting on nucleosomes by polycomb repressive complexes and on chromatin by SWI/SNF complexes on nucleosome assembly/disassembly, as well as main mutated genes linked to cancers, are reviewed. Among enzymes acting on histones and other proteins erasing the reversible modifications are histone deacetylases (HDACs). Sirtuins are of interest since most of these enzymes not only deacylate histones and other proteins, but also post-translationally modify proteins adding a Mono-ADP-ribose (MAR) moiety. MAR can be read by MACRO-domain containing proteins such as histone MacroH2A1, with specific function in chromatin assembly. Finally, recent advances are presented on non-coding RNAs with a scaffold function, prospecting their role in assembly of chromatin modifying complexes, recruiting enzyme players to chromatin regions. Lastly, the imbalance in metabolites production due to mitochondrial dysfunction is presented, with the potential of these metabolites to inhibit enzymes, either writers, readers or erasers of epitranscriptome marks. In the perspectives, studies are overwied on drugs under development aiming to limit excessive enzyme activities and to reactivate chromatin modifying complexes, for therapeutic application. This knowledge may lead to novel drugs and personalised medicine for cancer patients.
journal_name
Semin Cancer Bioljournal_title
Seminars in cancer biologyauthors
Farooqi AA,Fayyaz S,Poltronieri P,Calin G,Mallardo Mdoi
10.1016/j.semcancer.2020.07.013subject
Has Abstractpub_date
2020-07-30 00:00:00eissn
1044-579Xissn
1096-3650pii
S1044-579X(20)30170-Xpub_type
杂志文章abstract：:Mucins are large molecular weight glycoproteins characterized by carbohydrate sugars attached via 'O-glycosidic' linkages to serine or threonine. Mucins are synthesized by a variety of epithelial tissues as membrane-bound or secreted proteins, encoded by several distinct mucin genes. Numerous alterations of mucin-asso...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1991-12-01 00:00:00
abstract：:The two major breast cancer susceptibility genes, BRCA1 and BRCA2, account for the majority of familial breast-ovarian cancer, but only a modest proportion of breast cancer families without ovarian or male breast cancer. Search for additional breast cancer genes with traditional linkage analysis has so far been unsucc...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.2001.0393
更新日期：2001-10-01 00:00:00
abstract：:DNA copy number amplifications activate oncogenes and are found in the majority of advanced solid tumors. Cell-lineage specificity and oncogene affinity of DNA amplifications in cancer suggest that properties of precursor stem cells and selection pressure in the tissue micro-environment determine the genomic location ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2006.10.005
更新日期：2007-02-01 00:00:00
abstract：:Raf-1 belongs to a family of serine/threonine protein kinases which are highly conserved through evolution in multicellular organisms. Raf-1 kinase has gained much attention due to its function as a critical shuttle enzyme that connects stimulation of growth factor receptors and protein kinase C at the cell membrane t...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1994-08-01 00:00:00
abstract：:Close international collaboration between pediatric oncologists has led to marked improvements in the cure of patients, seen as a long-term overall survival rate of about 80%. Despite this progress, neuroblastoma remains a challenging disease for both clinicians and researchers. Major clinical problems include lack of...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2011.07.002
更新日期：2011-10-01 00:00:00
abstract：:Malignant mesothelioma, a tumor of the pleura, pericardium, and peritoneum, is presently a worldwide problem. Current therapy is ineffective in slowing the course of the disease, and median survival from the time of diagnosis is rarely greater than 1 year. While the tumor was almost unknown prior to the second half of...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.2000.0347
更新日期：2001-02-01 00:00:00
abstract：:Amino-bisphosphonates (N-BPs) have been commercially available for over four decades and are used for the treatment of osteoporosis, Paget's disease, hypercalcemia of malignancy, and bone metastases derived from various cancer types. Zoledronate and alendronate, two of the most potent N-BPs, have demonstrated direct t...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.12.001
更新日期：2019-12-23 00:00:00
abstract：:Prostate cancer (PCa), a hormonally-driven cancer, ranks first in incidence and second in cancer related mortality in men in most Western industrialized countries. Androgen and androgen receptor (AR) are the dominant modulators of PCa growth. Over the last two decades multiple advancements in screening, treatment, sur...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2016.06.003
更新日期：2016-10-01 00:00:00
abstract：:In the setting of cancer pathology, molecular characterization of tumors providing diagnostic and predictive information is acquiring more and more relevance. Moreover, the advent of innovative technologies continuously improves the knowledge of the molecular landscape of tumors and strengthens the links between clini...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.10.004
更新日期：2020-10-19 00:00:00
abstract：:Recent empirical data have elucidated a compelling physiological basis for endogenously expressed, chemically authentic, morphine and its cognate mu3 and mu4 opiate receptors. Cellular "morphinergic" signaling is predominantly targeted to autocrine/paracrine regulatory processes and is reciprocally linked to stimulate...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2007.12.001
更新日期：2008-06-01 00:00:00
abstract：:Uveal melanoma (UM) is a type of intraocular tumor with a propensity to disseminate to the liver. Despite the identification of the early driver mutations during the development of the pathology, the process of UM metastasis is still not fully comprehended. A better understanding of the genetic, molecular, and environ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章
doi：10.1016/j.semcancer.2020.05.003
更新日期：2020-05-22 00:00:00
abstract：:Breast cancer is one of the most prevalent and reoccurring cancers and the second most common reason of death in women. Despite advancements in therapeutic strategies for breast cancer, early tumor recurrence and metastasis in patients indicate resistance to chemotherapeutic medicines, such as paclitaxel due to the ab...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.12.022
更新日期：2019-12-28 00:00:00
abstract：:Prostate specific antigen (PSA) is serine protease produced at high concentrations by normal and malignant prostatic epithelium. It is mainly secreted into seminal fluid, where it digests the gel forming after ejaculation. Only minor amounts of PSA leak out into circulation from the normal prostate, but the release of...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1998.0086
更新日期：1999-04-01 00:00:00
abstract：:Managing cancer is now one of the biggest concerns of health organizations. Many strategies have been developed in drug discovery pipelines to help rectify this problem and two of the best ones are drug repurposing and computational methods. The combination of these approaches can have immense impact on the course of ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.04.007
更新日期：2020-04-28 00:00:00
abstract：:Liver cancer is the fifth most common cancer and the third most common cause of cancer related death in the world. The recent development of new techniques for the investigations of global change in the gene expression, signaling pathways and wide genome binding has provided novel information for the mechanisms underl...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2010.09.001
更新日期：2011-02-01 00:00:00
abstract：:Neutrophils in the tumor host may promote tumor progression by enhancing angiogenesis, invasion and metastasis. Granulocytic myeloid-derived suppressor cells (MDSC) share many features with neutrophils. Classically, MDSC are viewed as and defined as immunosuppressive cells. In this article we summarize and critically ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2013.02.007
更新日期：2013-06-01 00:00:00
abstract：:T cell acute leukaemias involve a number of different classes of oncogenes. A group of such genes is the RBTN family located on chromosomes 11 and 12. Two members of this family, RBTN1/Ttg-1 and RBTN2/Ttg-2, are located near recurring T cell acute lymphocytic leukaemia-associated translocations. Chromosomal translocat...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1993-12-01 00:00:00
abstract：:Abnormally activated RAS proteins are the main oncogenic driver that governs the functioning of major signaling pathways involved in the initiation and development of human malignancies. Mutations in RAS genes and or its regulators, most frequent in human cancers, are the main force for incessant RAS activation and as...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2018.03.001
更新日期：2019-02-01 00:00:00
abstract：:Tumor masses are deprived of oxygen and characterized by enhanced glucose uptake followed by glycolysis. Elevated glucose levels induce non-enzymatic glycosylation or glycation of proteins which leads to accumulation of advanced glycation end products (AGE). These AGE molecules bind to their respective receptors calle...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2017.05.008
更新日期：2018-04-01 00:00:00
abstract：:The discovery of microRNAs (miRNAs) is one of the major scientific breakthroughs in recent years and has revolutionized the way we look at gene regulation. Although we are still at a very early stage in understanding their impact on immunity, miRNAs are changing the way we think about the development of the immune sys...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2008.01.005
更新日期：2008-04-01 00:00:00
abstract：:The growth regulatory functions of a family of structurally related polypeptides are mediated through the membrane-bound epidermal growth factor receptor molecule. This ligand family includes epidermal growth factor, transforming growth factor-alpha, amphiregulin, and polypeptides encoded by several poxviruses. The st...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1990-08-01 00:00:00
abstract：:A low vitamin D status is associated with an increased risk of various cancers, such as of colon, breast, prostate and hematological cells. The biologically most active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a high affinity ligand of the transcription factor vitamin D receptor (VDR). 1,25(OH)2...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.05.018
更新日期：2020-05-30 00:00:00
abstract：:Bone marrow transplantation is currently used to treat a variety of life-threatening diseases. Its applications could be expanded if the risks of graft-versus-host disease (GVHD), a complex pathologic disease, could be reduced. Immunotoxins may provide a means to control drug refractory GVHD. This article will discuss...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1996.0009
更新日期：1996-04-01 00:00:00
abstract：:Patients with HIV infection are at increased risk of developing non-Hodgkin lymphoma and Hodgkin lymphoma. While the pathogenesis of these lymphomas is incompletely understood, evidence indicates that immune deregulation, genetic alterations and cytokine production play an important role in HIV lymphomagenesis. The ly...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2015.06.002
更新日期：2015-10-01 00:00:00
abstract：:Breast cancer is the most common female malignancy and a major cause of death in middle-aged women. A positive family history of breast cancer is one of the strongest risk factors for the disease. In addition, many afflicted breast cancer families are characterized by early onset and bilateral tumors, and also, in som...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.2000.0325
更新日期：2000-08-01 00:00:00
abstract：:Circular RNAs (circRNAs) are a class of single-stranded closed non-coding RNA molecules (ncRNAs), which are formed as a result of reverse splicing of mRNAs. Despite their relative abundance, an interest in understanding their regulatory importance is rather recent. High stability, abundance and evolutionary conservati...
journal_title：Seminars in cancer biology
pub_type： 杂志文章
doi：10.1016/j.semcancer.2020.12.026
更新日期：2021-01-09 00:00:00
abstract：:The HLA-G gene gives rise to six differently spliced mRNAs. The membrane bound HLA-G1 molecule containing all three extracellular domains presents peptides that follow motif requirements similar to those of classical HLA class I molecules. This isoform is also capable of inhibiting Natural Killer (NK) cells, but is on...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1998.0105
更新日期：1999-02-01 00:00:00
abstract：:Exosomes are small membrane vesicles with a size ranging from 40 to 100nm. They can serve as functional mediators in cell interaction leading to cancer metastasis. Metastasis is a complex multistep process of cancer cell invasion, survival in blood vessels, attachment to and colonization of the host organ. Exosomes in...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2017.02.006
更新日期：2017-06-01 00:00:00
abstract：:Small cell lung cancer (SCLC) is a particular subtype of lung cancer with high mortality. Recent advances in understanding SCLC genomics and breakthroughs of immunotherapy have substantially expanded existing knowledge and treatment modalities. However, challenges associated with SCLC remain enigmatic and elusive. Mos...
journal_title：Seminars in cancer biology
pub_type： 杂志文章
doi：10.1016/j.semcancer.2020.11.006
更新日期：2020-11-18 00:00:00
abstract：:Disseminated tumor cells are present in many patients at diagnosis. At a time when the disseminated disease becomes prominent, patients have already been treated with many cycles of therapy to which their metastases were also exposed. These metastases have genetically evolved from primary tumors. Furthermore, their in...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2012.03.005
更新日期：2012-06-01 00:00:00
