Potential Therapeutic Applications of MDA-9/Syntenin-NF-κB-RKIP Loop in Human Liver Carcinoma.

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 presence of a regulation loop like that between MDA-9/Syntenin - NF-κB - RKIP in human liver carcinoma. METHODS:Transient transfection was performed with siRNA anti-MDA-9/Syntenin. Expression of different factors was evaluated by Real time-PCR and Western blotting, while NF-κB activation by TransAM assay. Invasion capacity was analyzed by Matrigel Invasion Assay and the effects of agents on cell viability were examined by MTS assay. RESULTS:We have examined basal expression of MDA-9/Syntenin in three cell lines of human liver carcinoma (HA22T/VGH, Hep3B and HepG2). In all cell lines there was an inverse relationship between MDA-9/Syntenin and RKIP expression levels, and a positive correlation between MDA-9/Syntenin expression and NF-κB activation levels. By silencing with a siRNA anti-MDA-9/Syntenin we observed in all cell lines a very strong increase of RKIP at mRNA level. Interestingly, in all cell lines, inhibition of MDA- 9/Syntenin expression induced NF-κB downregulation and contemporary a reduction in invasion ability MMP-2 dependent. Finally, we showed a good additive effect of MDA- 9/Syntenin siRNA when associated with Curcumin or Doxorubicin on cell growth inhibition. CONCLUSION:Our data confirm the key role of MDA-9/Syntenin in HCC biology. The presence of a regulation loop among MDA-9/Syntenin, NF-κB and RKIP provide new pharmacological approaches.

journal_name

Curr Mol Med

authors

Notarbartolo M,Labbozzetta M,Pojero F,D'Alessandro N,Poma P

doi

10.2174/1566524019666190104105043

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

630-639

issue

9

eissn

1566-5240

issn

1875-5666

pii

CMM-EPUB-95591

journal_volume

18

pub_type

杂志文章
  • Plasma membrane electron transport: a new target for cancer drug development.

    abstract::The view that mitochondrial electron transport is the only site of aerobic respiration and the primary bioenergetic pathway in mammalian cells is well established in the literature. Although this paradigm is widely accepted for most tissues, the situation is less clear for proliferating cells. Increasing evidence indi...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652406779010777

    authors: Herst PM,Berridge MV

    更新日期:2006-12-01 00:00:00

  • The many faces of glutathione transferase pi.

    abstract::Glutathione transferase Pi (GST-pi, GSTP) is known to strongly affect human susceptibility to several cancers, asthma and neurodegenerative disorders. As with other glutathione transferases, it catalyses the addition of reduced glutathione to electrophilic species, and it is important in metabolite detoxification. It ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652411794859278

    authors: Vasieva O

    更新日期:2011-03-01 00:00:00

  • Aging and Proteins: What Does Proteostasis Have to Do with Age?

    abstract::The world is aging and we must face the challenges that this brings. One of the reasons for the increasing aging of the world's population is the increase in life expectancy and, since we live longer, it is of paramount importance to live well and to prevent age-associated diseases. In this way, it is crucial to impro...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524018666180907162955

    authors: Magalhaes S,Goodfellow BJ,Nunes A

    更新日期:2018-01-01 00:00:00

  • Protein serine/threonine phosphotase-1 is essential in governing normal development of vertebrate eye.

    abstract::Protein serine/threonine phosphatase-1 (PP-1) is one of the key enzymes responsible for dephosphorylation in vertebrates. Protein dephosphorylation via PP-1 is implicated in many different biological processes including gene expression, cell cycle control, transformation, neuronal transmission, apoptosis, autophage an...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/156652412803833535

    authors: Liu WB,Yan Q,Liu FY,Tang XC,Chen HG,Liu J,Nie L,Zhang XW,Ji WK,Hu XH,Hu WF,Woodward Z,Wu KL,Wu MX,Liu XL,Luo LX,Yu MB,Liu YZ,Liu SJ,Li DW

    更新日期:2012-12-01 00:00:00

  • The Impact of CRISPR/Cas9-Based Genomic Engineering on Biomedical Research and Medicine.

    abstract::There has been prolonged and significant interest in manipulating the genome for a wide range of applications in biomedical research and medicine. An existing challenge in realizing this potential has been the inability to precisely edit specific DNA sequences. Past efforts to generate targeted double stranded DNA cle...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524016666160316150847

    authors: Go DE,Stottmann RW

    更新日期:2016-01-01 00:00:00

  • Immunity to systemic Salmonella infections.

    abstract::Salmonella infections are a serious public health problem in developing countries and represent a constant concern for the food industry. The severity and the outcome of a systemic Salmonella infection depends on the "virulence" of the bacteria, on the infectious dose as well as on the genetic makeup and immunological...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524023362492

    authors: Mastroeni P

    更新日期:2002-06-01 00:00:00

  • Autophagy: for better or for worse, in good times or in bad times.

    abstract::Autophagy is a bulk cytosolic degradative process which in the last few years has become a key pathway for the advancement of molecular medicine. Autophagy (cellular self-eating) has several implications in human disorders involving accumulation of cytosolic protein aggregates such as Alzheimer, Parkinson, Huntington ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652408783769634

    authors: Lerena C,Calligaris SD,Colombo MI

    更新日期:2008-03-01 00:00:00

  • Orexigenic/anorexigenic signals in bulimia nervosa.

    abstract::Bulimia nervosa (BN) and Anorexia Nervosa (AN) are currently classified as eating disorders (ED). Both disorders are the product of complex interaction between physiological and psychological and social processes; they are characterized by abnormal eating behavior. However, patients with BN differ from AN in their nut...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524033479762

    authors: Takimoto Y,Inui A,Kumano H,Kuboki T

    更新日期:2003-06-01 00:00:00

  • Telomere maintenance and tumorigenesis: an "ALT"ernative road.

    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

    authors: Stewart SA

    更新日期:2005-03-01 00:00:00

  • Current molecular understanding and future treatment strategies for pathologic ocular neovascularization.

    abstract::The leading cause of blindness in the developed world results from several disorders that have pathologic ocular neovascularization as the common pathway leading to vision loss. These disorders include exudative age related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), retina...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652409789712783

    authors: Tolentino MJ

    更新日期:2009-11-01 00:00:00

  • Suppression of NF-κB activation by gentian violet promotes osteoblastogenesis and suppresses osteoclastogenesis.

    abstract::Skeletal mass is regulated by the coordinated action of bone forming osteoblasts and bone resorbing osteoclasts. Accelerated rates of bone resorption relative to bone formation lead to net bone loss and the development of osteoporosis, a devastating disease that predisposes the skeleton to fractures. Bone fractures ar...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524014666140724104842

    authors: Yamaguchi M,Vikulina T,Arbiser JL,Weitzmann MN

    更新日期:2014-01-01 00:00:00

  • Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP): novel regulators of Ca2+-signaling and cell function.

    abstract::Ca2+ ions are involved in the regulation of many diverse functions in animal and plant cells, e.g. muscle contraction, secretion of neurotransmitters, hormones and enzymes, fertilization of oocytes, and lymphocyte activation and proliferation. The intracellular Ca2+ concentration can be increased by different molecula...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524024605707

    authors: Guse AH

    更新日期:2002-05-01 00:00:00

  • The study of HLA class II and autoimmune diabetes.

    abstract::Many autoimmune diseases have genetic associations with the Major Histocompatibility Complex (MHC) class II loci. Susceptibility to Type 1 diabetes mellitus (TIDM) is particularly associated with Human Leucocyte Antigen (HLA) DR3, 4 and associated DQ2, 8 alleles and this is well documented in genetic association studi...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524033361591

    authors: Wong FS,Wen L

    更新日期:2003-02-01 00:00:00

  • Apoptosis and oxidative stress-related diseases: the p66Shc connection.

    abstract::p66Shc is the only known proapoptotic member of the Shc protein family of molecular adaptors. Through its redox activity, p66Shc oxidates cytochrome-c, leading to increased ROS production and, eventually, to apoptosis. p66Shc has been implicated in the control of oxidative stress and life span in mammals. In this revi...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652409787847254

    authors: Pellegrini M,Baldari CT

    更新日期:2009-04-01 00:00:00

  • Mesenchymal stem cells regulate cytoskeletal dynamics and promote cancer cell invasion through low dose nitric oxide.

    abstract::Bone marrow-derived mesenchymal stem cells (BMSCs) can be recruited to tumor sites and integrate into the stroma of tumors. When co-cultured with BMSCs, otherwise weakly metastatic nasopharyngeal carcinoma cells (NPC) showed improved metastatic ability. BMSCs in the tumor environment displayed the characteristics of m...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524014666140724102301

    authors: Zhang L,Sun J,Liu Z,Dai Y,Luo Z,Jiang X,Li Z,Li Y,Cao P,Zhou Y,Zeng Z,Tang A,Li X,Li X,Xiang J,Li G

    更新日期:2014-01-01 00:00:00

  • Mechanisms of liver injury: an overview.

    abstract::Liver cirrhosis, an end-result of a wide variety of the liver diseases, is a world wide health problem. Because of its unique organ system, i.e., portal blood supply, bile formation and enterohepatic circulation, drug metabolism system, and sinusoidal lining cells such as Kupffer, endothelial and stellate cells, the l...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524033479528

    authors: Higuchi H,Gores GJ

    更新日期:2003-09-01 00:00:00

  • Clinical and genetic features of Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) syndrome.

    abstract::WHIM syndrome is a dominantly inherited primary immunodeficiency disorder representing the first identified example of human disease caused by mutations in the gene encoding for the chemokine receptor CXCR4. Pathogenesis is mediated by CXCR4 hyperfunction, leading to increased responsiveness to its unique ligand CXCL1...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652411795677963

    authors: Dotta L,Tassone L,Badolato R

    更新日期:2011-06-01 00:00:00

  • Bacteriocins: New Potential Therapeutic Candidates in Cancer Therapy.

    abstract::Cancer is one of the most important disorders which is associated with high mortality and high costs of treatment for patients. Despite several efforts, finding, designing and developing, new therapeutic platforms in treatment of cancer patients are still required. Utilization of microorganisms particularly bacteria h...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524020999200817113730

    authors: Fathizadeh H,Saffari M,Esmaeili D,Moniri R,Kafil HS

    更新日期:2020-08-17 00:00:00

  • Von Hippel-Lindau disease.

    abstract::Germline mutations in the VHL tumour suppressor gene may cause a variety of phenotypes including von Hippel-Lindau (VHL) disease, familial phaeochromocytoma and inherited polycythaemia. VHL disease is a multisystem familial cancer syndrome and is the commonest cause of familial renal cell carcinoma (RCC). VHL disease ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524043359827

    authors: Maher ER

    更新日期:2004-12-01 00:00:00

  • Molecular imaging of brain tumors personal experience and review of the literature.

    abstract::Non-invasive energy metabolism measurements in brain tumors in vivo are now performed widely as molecular imaging by positron emission tomography. This capability has developed from a large number of basic and clinical science investigations that have cross fertilized one another. Apart from precise anatomical localiz...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652408786733766

    authors: Schaller BJ,Cornelius JF,Sandu N,Buchfelder M

    更新日期:2008-12-01 00:00:00

  • Charcot-Marie-Tooth Disease and Related Hereditary Neuropathies: From Gene Function to Associated Phenotypes.

    abstract::Charcot-Marie-Tooth disease (CMT) and related neuropathies are a genetically highly heterogeneous group of neurodegenerative disorders. CMT affects both the sensory and motor nerves, distal Hereditary Motor Neuropathies (dHMN) are phenotypically similar disorders involving only motor nerves, while Hereditary Sensory a...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524014666141010154205

    authors: Pareyson D,Saveri P,Piscosquito G

    更新日期:2014-01-01 00:00:00

  • Reprograming Carcinoma Associated Fibroblasts by microRNAs.

    abstract::Carcinoma-associated fibroblasts (CAFs) are activated fibroblasts during development of several cancer types, and therefore emerge as an attractive therapeutic target for cancer therapy. Drugs such as PT-100 and sibrotuzumab that block the functions of CAFs have already been in clinical trials. However, these drugs ex...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524018666171205113959

    authors: Xu Y,Zhou X,Mei M,Ren Y

    更新日期:2017-01-01 00:00:00

  • PRAME/EZH2-mediated regulation of TRAIL: a new target for cancer therapy.

    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

    authors: De Carvalho DD,Mello BP,Pereira WO,Amarante-Mendes GP

    更新日期:2013-02-01 00:00:00

  • cAMP signalling in the kinetoplastid protozoa.

    abstract::Several species of kinetoplastid protozoa cause major human infectious diseases. Trypanosoma cruzi is responsible for the fatal Chagas disease in large parts of South America, the various species of Leishmania cause a number of different human diseases with millions of patients world-wide, and the African trypanosome ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524043360113

    authors: Seebeck T,Schaub R,Johner A

    更新日期:2004-09-01 00:00:00

  • Potentialities of induced pluripotent stem (iPS) cells for treatment of diseases.

    abstract::Induced pluripotent stem (iPS) cell research has been growing a new height throughout the world due to its potentialities in medical applications. We can explore several therapeutic applications through the iPS cell research. In this review, we have first discussed the development of iPS cells, reprogramming factors, ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652410793384178

    authors: Chakraborty C,Shah KD,Cao WG,Hsu CH,Wen ZH,Lin CS

    更新日期:2010-11-01 00:00:00

  • Hematopoietic stem cells: transcriptional regulation, ex vivo expansion and clinical application.

    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

    authors: Aggarwal R,Lu J,Pompili VJ,Das H

    更新日期:2012-01-01 00:00:00

  • Apoptosis: its functions and control in the ocular lens.

    abstract::The ocular lens is a non-vascular and non-innervated transparent organ that plays an important role in vision processing. This unique organ is derived from the embryonic ectoderm of the brain region through a complicated differentiation process in which apoptosis plays a key role. First, when the committed ectoderm be...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652410793937741

    authors: Zhang L,Yan Q,Liu JP,Zou LJ,Liu J,Sun S,Deng M,Gong L,Ji WK,Li DW

    更新日期:2010-12-01 00:00:00

  • Specific Roles of NMDA Receptor Subunits in Mental Disorders.

    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

    authors: Yamamoto H,Hagino Y,Kasai S,Ikeda K

    更新日期:2015-01-01 00:00:00

  • Osteopontin: an effector and an effect of tumor metastasis.

    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

    authors: Shevde LA,Das S,Clark DW,Samant RS

    更新日期:2010-02-01 00:00:00

  • Medullary thyroid cancer: a promising model for targeted therapy.

    abstract::In recent years, the clinical validation of molecular targeted therapies inhibiting the action of pathogenic tyrosine kinase (TK) has been one of the most exciting developments in cancer research. In this context, medullary thyroid carcinoma (MTC) represents a promising model. It is well known that in MTC, the RET rec...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652410792630607

    authors: Torino F,Paragliola RM,Barnabei A,Corsello SM

    更新日期:2010-10-01 00:00:00