Abstract:
:Extracellular matrices (ECMs) are dynamic structures that provide cells not only with a structural support but, importantly, exhibit significant functional roles in the control of key cellular events such as adhesion, migration, proliferation, differentiation, and survival. In tumors, matrix effectors such as proteoglycans (PGs) and matrix metalloproteinases (MMPs) constitute major regulators of the interactions between tumor cells and their microenvironment and, therefore, they have been identified as potential molecular targets that are expected to advance the pharmacological treatment of cancer. ECMs composition is highly affected by cells through intrinsic regulatory mechanisms, such as the ubiquitin-proteasome system (UPS). Proteasome is a major cellular protease complex that controls the concentration and turnover of molecules in ECMs, including certain types of PGs, MMPs and collagens, and consequently, in the tumor microenvironment. Furthermore, proteasome activity is regulated by PG-derived intracellular glycosaminoglycan moieties revealing a critical inter-dependence of these compounds. Since ECMs renewal and degradation can be tightly regulated by proteasome activities, its modulation may be considered as a novel strategy to control the properties of tumor microenvironment. Currently, there are several proteasome inhibitors targeting distinct molecular pathways either approved or in clinical trials for the treatment of multiple cancers. In this review, the novel approach of targeting the proteasome to selectively regulate the synthesis and the bioactivity of certain matrix PGs and MMPs is presented and discussed.
journal_name
Curr Mol Medjournal_title
Current molecular medicineauthors
Skandalis SS,Aletras AJ,Gialeli C,Theocharis AD,Afratis N,Tzanakakis GN,Karamanos NKdoi
10.2174/156652412802480943subject
Has Abstractpub_date
2012-09-01 00:00:00pages
1068-82issue
8eissn
1566-5240issn
1875-5666pii
CMM-EPUB-20120605-9journal_volume
12pub_type
杂志文章,评审abstract::The acquisition of cellular immortality is a critical step in human tumorigenesis. While the vast majority of human tumors activate the catalytic component of telomerase (hTERT) to stabilize their telomeres and attain immortality, a significant portion (7-10%) utilize a poorly defined alternative form of telomere main...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524053586653
更新日期:2005-03-01 00:00:00
abstract::The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exerts a cancer cell-specific pro-apoptotic activity. This property made the TRAIL associated pathway one of the most promising strategies aimed at inducing tumor-selective death. In fact, several approaches have been considered to explore this pathwa...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652413804810727
更新日期:2013-02-01 00:00:00
abstract::Antibody targeted cytoplasmic delivery of drugs is difficult to achieve as antigen-antibody interaction results in the payload being directed to the endosomal compartment. However, Sendai viral envelopes can bring about cytoplasmic delivery due to F-protein mediated membrane fusion. In this study we have generated and...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524015666150505155949
更新日期:2015-01-01 00:00:00
abstract::Osteopontin (OPN) is a matricellular protein that is produced by multiple tissues in our body and is most abundant in bone. It is also produced by cancer cells and plays a determinative role in the growth, progression and metastasis of cancer. Clinically, OPN has been reported to be upregulated in tumor cells per se; ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652410791065381
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:Photoreceptor cell death is a key pathology of retinal degeneration diseases. To date, the molecular mechanisms for this pathological process remain largely unclear. Junctional adhesion molecule-c (Jam-c) has been shown to play important roles in different biological events. However, its effect on retinal ne...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524018666180212144500
更新日期:2018-03-09 00:00:00
abstract::Maintenance of ex vivo hematopoietic stem cells (HSC) pool and its differentiated progeny is regulated by complex network of transcriptional factors, cell cycle proteins, extracellular matrix, and their microenvironment through an orchestrated fashion. Strides have been made to understand the mechanisms regulating in ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652412798376125
更新日期:2012-01-01 00:00:00
abstract::Many potential HIV vaccine strategies are being explored in both animal model and human settings. The success of any vaccine relies on relevant antigenic determinants being presented to the immune system for the activation of broad and long-lasting immunity. Effective immunity against HIV infection will likely require...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524033479870
更新日期:2003-05-01 00:00:00
abstract::The blood stage of the malaria parasite's life cycle is responsible for all the clinical symptoms of malaria. The development of clinical disease is dependent on the interplay of the infecting parasite with the immune status and genetic background of the host. Following repeated exposure to malaria parasites, individu...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652406776055212
更新日期:2006-03-01 00:00:00
abstract::Eicosanoids are diverse mediators of inflammation that derive from a single cell membrane phospholipid-associated precursor, arachidonic acid. This precursor is metabolized to several groups of lipid mediators, including (but not limited to) prostaglandins, leukotrienes, and lipoxins, in a tightly regulated, coordinat...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652408785160989
更新日期:2008-08-01 00:00:00
abstract:BACKGROUND:Overexpression of MDA-9/Syntenin occurs in multiple human cancer cell lines and is associated with higher grade of tumor classification, invasiveness and metastasis. In some cases, its role in cancer biology depends on relationships between MDA-9/Syntenin and NF-κB. OBJECTIVE:This study aims to analyze the ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190104105043
更新日期:2018-01-01 00:00:00
abstract::N-methyl-D-aspartate (NMDA) receptor plays important roles in learning and memory. NMDA receptors are a tetramer that consists of two glycine-binding subunits GluN1, two glutamate-binding subunits (i.e., GluN2A, GluN2B, GluN2C, and GluN2D), a combination of a GluN2 subunit and glycine-binding GluN3 subunit (i.e., GluN...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524015666150330142807
更新日期:2015-01-01 00:00:00
abstract::Pancreatic and duodenal homeobox-1 (PDX-1) is a homeodomain-containing transcription factor that plays a critical role in pancreatic development, β-cell differentiation, maintenance of normal β-cell function and tumorigenesis. PDX-1 is subjected to extensive post-translational modifications for its stability, subcellu...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:
更新日期:2013-03-01 00:00:00
abstract::Despite advances in biomedical sciences, the prognosis of patients with brain tumors remains poor. Effective treatment is lacking for these central nervous system (CNS) cancers. Targeted immunotoxins are a new class of therapeutic approaches that have emerged for the treatment of human cancers. In this approach, tumor...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409788970661
更新日期:2009-08-01 00:00:00
abstract::Transmissible Spongiform Encephalopathies or prion related disorders are fatal and infectious neurodegenerative diseases characterized by extensive neuronal apoptosis and accumulation of a misfolded form of the cellular prion protein (PrP), denoted PrP(Sc). Although the mechanism of neurodegeneration and the involveme...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043360654
更新日期:2004-06-01 00:00:00
abstract::Glycogen is a branched polymer of glucose which serves as a reservoir of glucose units. The two largest deposits in mammals are in the liver and skeletal muscle but many cells are capable synthesizing glycogen. Its accumulation and utilization are under elaborate controls involving primarily covalent phosphorylation a...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524024605761
更新日期:2002-03-01 00:00:00
abstract:OBJECTIVES:Celastrol, a quinone methide triterpenoid, could induce apoptosis in pancreatic cancer cells. The purpose of this study is to determine whether there is protective autophagy after celastrol treatment in pancreatic cancer cells and the synergistic effects of celastrol and 3-MA in vitro and in vivo. METHODS:T...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524014666140414211223
更新日期:2014-05-01 00:00:00
abstract::Hypoxia is a major hallmark of the tumor microenvironment that is strictly associated with rapid cancer progression and induction of metastasis. Hypoxia inhibits disulfide bond formation and impairs protein folding in the Endoplasmic Reticulum (ER). The stress in the ER induces the activation of Unfolded Protein Respo...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524016666160523143937
更新日期:2016-01-01 00:00:00
abstract::Interleukin-25 (IL-25) plays a key role in the initiation and expansion of T helper (Th) 2 cell-mediated immune responses, thereby contributing to allergic diseases and host defense against helminthic parasites. More recent studies have however shown that IL-25 can also control the function of non-T cells, such as ant...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411794474365
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:Colorectal cancer (CRC) is the third most common cancer worldwide and the third leading cause of cancer-related death. It is a heterogeneous disease that develops through different genetic and epigenetic mechanisms. To date, no comprehensive systematic review investigating genetic risk factors for familial a...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666191014170136
更新日期:2020-01-01 00:00:00
abstract:PURPOSE:Retinal ganglion cells (RGCs) apoptosis is a common characteristic of optic neuropathies. p53-induced protein with a death domain (PIDD) is a well-known regulator of genotoxic stress-induced apoptosis, which is constitutively cleaved into three main fragments: PIDD-N, PIDD-C and PIDD-CC. Thus, we aim to determi...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190918160032
更新日期:2019-01-01 00:00:00
abstract::Pluripotent stem cells (PSCs) are powerful tools for studying developmental biology and neuronal diseases. Conventional differentiation protocols require several intermediate states and different culture conditions, inefficiently generating mixed subtypes of neuronal cells with immature characteristics. Direct program...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200421115251
更新日期:2020-04-21 00:00:00
abstract::After several years of controversy, antibodies (Abs) are now believed to play an important role in the protection against fungal infections. Among them, recent data are strongly supporting the relevance of protective yeast killer toxin-like Abs ("antibiobodies", KT-Abs), which are able to exert a direct microbicidal a...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524054022558
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND:In vertebrates, cilium is crucial for Hedgehog signaling transduction. Forkhead box transcriptional factor FoxF1 is reported to be associated with Sonic Hedgehog (Shh) signaling in many cases. However, the role of FoxF1 in cilium remains unknown. Here, we showed an essential role of FoxF1 in the regulation o...
journal_title:Current molecular medicine
pub_type: 信件
doi:10.2174/1566524019666190405115420
更新日期:2019-01-01 00:00:00
abstract::Although surgery and radiotherapy are highly efficient in local tumor control, distal metastases and tumor recurrence often limit therapeutic outcome. It is becoming progressively more evident that curative tumor therapy depends on the presence and maintenance of an intact immune system which has the capacity to elici...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652412803306666
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND:Persistent hyperlactatemia is associated with greater mortality in shock. Liver is the main site of lactate metabolism. METHOD:In the first part, freshly isolated hepatocytes were incubated in 10% fetal bovine serum William's E medium supplemented with 10 mM lactate. Cells were then exposed to 100 μM ursode...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200123161340
更新日期:2020-01-01 00:00:00
abstract::As an MHC class I protein, the disease association of HLA-B27 with inflammatory arthritis has been widely assumed to imply a role for the T cell antigen receptor (TCR) in disease. However, in addition to their classical antigen-presenting role, HLA class I proteins are recognised by members of the killer immunoglobuli...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043479329
更新日期:2004-02-01 00:00:00
abstract::The central role of glutamate receptors in mediating excitotoxic neuronal death in stroke, epilepsy and trauma has been well established. Glutamate is the major excitatory amino acid transmitter within the CNS and it's signaling is mediated by a number of postsynaptic ionotropic and metabotropic receptors. Although ca...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043479202
更新日期:2004-03-01 00:00:00
abstract::Genome-wide association studies (GWAS) have become increasingly widely used to determine regions of the genome which may contain loci influencing the risk of neurological disorders. While linkage studies have identified genes that cause a number of Mendelian disorders, linkage analysis is less well suited for the more...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409789105534
更新日期:2009-09-01 00:00:00
abstract::The unexpected encounter between the fields of HIV and chemokines has opened new perspectives for understanding the mechanisms of AIDS pathogenesis, as well as for the development of effective therapies and vaccines. Selected chemokines act as potent natural inhibitors of HIV infection, as they bind and downmodulate c...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524023361862
更新日期:2002-12-01 00:00:00
abstract:BACKGROUND:Macrophages undergo polarization or activation in response to environmental stimuli, an essential process for proper immune response. Meanwhile, excessive activation of macrophages causes autoimmune diseases. It is therefore crucial to prevent over-activation of macrophage in order to maintain the proper imm...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524017666171106114537
更新日期:2017-12-07 00:00:00