Abstract:
:G-protein-coupled receptor (GPCR)-related proteins are dysregulated and the GPCR CC-chemokine receptor 10 (CCR10) is significantly upregulated in inflammation-driven HCC. However, CCR10's role in inflammation-driven hepatocarcinogenesis remains unknown. The aim of this study was to evaluate the role of CCR10 in inflammation-driven hepatocarcinogenesis. Via a targeted gene expression microarray screening alterations in GPCR family gene expression, we found CCR10 to be significantly upregulated in hepatocytes isolated from inflammation-driven human HCC tumors and matching paracancerous tissues. Tetrachloromethane (CCl4)-induced and diethylnitrosamine (DEN)-induced murine models of inflammatory hepatocarcinogenesis displayed significant hepatocellular TNF and CCR10 upregulation. Exogenous TNF applied to HepG2 and LO2 cell lines as well as wild-type (WT) mice significantly upregulated hepatocellular CCR10 expression, Akt phosphorylation, PCNA expression, and hepatocellular proliferation. Additionally, exogenous TNF significantly upregulated secretion of the natural CCR10 ligand-agonist CCL28 from both cell lines. Transgenic CCR10-knockout (CCR10 KO) in DEN-treated mice significantly increased hepatocellular apoptosis levels and significantly lowered compensatory hepatocellular proliferation but did not affect upstream TNF expression. In addition, DEN-treated CCR10 KO mice showed a significantly lower liver weight/body weight ratio, significantly lower liver tumor incidence, and significantly smaller tumors. Moreover, exogenous CCR10 expression significantly raised xenograft tumor growth in Balb/c nude mice. In vitro, CCR10 transfection or CCL28 treatment in HepG2 and LO2 cell lines significantly increased Akt phosphorylation, PCNA expression, and cell proliferation, while CCR10 silencing or Akt inhibition produced the opposite effects. In vivo, hepatocytes isolated from HCC tumor tissue and matching paracancerous tissue in DEN-treated CCR10 KO mice showed significantly lower Akt phosphorylation and PCNA expression relative to WT hepatocytes. In conclusion, inflammation-induced TNF promotes hepatocellular CCR10 expression and downstream PI3K/Akt-mediated hepatocarcinogenesis. CCR10 appears to function as a linkage between TNF stimulation and downstream PI3K/Akt pathway activation and shows promise as a potential therapeutic target for inflammation-driven HCC.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Wu Q,Chen JX,Chen Y,Cai LL,Wang XZ,Guo WH,Zheng JFdoi
10.1038/s41419-018-0267-9subject
Has Abstractpub_date
2018-02-14 00:00:00pages
232issue
2issn
2041-4889pii
10.1038/s41419-018-0267-9journal_volume
9pub_type
杂志文章abstract::Long non-coding RNAs (lncRNAs) play a vital role in tumourigenesis, including that of glioma. Small nucleolar RNA host gene 1 (SNHG1) is a relatively novel lncRNA that is involved in the development of multiple human tumours. However, its underlying molecular mechanism in glioma has not been completely clarified. In t...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1698-7
更新日期:2019-06-12 00:00:00
abstract::The sex-determining region Y (SRY)-box (SOX) family has a crucial role in carcinogenesis and cancer progression. However, the role of SOX12 and the mechanism by which it is dysregulated in colorectal cancer (CRC) remain unclear. Here we analyzed SOX12 expression patterns in two independent CRC cohorts (cohort I, n = 3...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1481-9
更新日期:2019-03-11 00:00:00
abstract::The development of nephrotoxicity largely limits the clinical use of chemotherapy. MiRNAs are able to target various genes and involved in the regulation of diverse cellular processes, including cell apoptosis and death. Our study showed that miR-181a expression was significantly increased after 5-fluorouracil (5-FU) ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0677-8
更新日期:2018-05-23 00:00:00
abstract::It is largely recognized that fibroblast activation protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) of many human carcinomas. Furthermore, FAP was recently also reported to be expressed in carcinoma cells of the breast, stomach, pancreatic ductal adenocarcinoma, colorectum, and uterine cervix. The c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.122
更新日期:2014-04-10 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease that is characterized by enhanced changes in stem cell differentiation and fibroblast proliferation. Resident mesenchymal stem cells (LR-MSCs) can undergo phenotype conversion to myofibroblasts to augment extracellular matrix producti...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0692-9
更新日期:2018-05-29 00:00:00
abstract::Previously, we confirmed that sphingosine kinase 1 (SphK1) inhibition improves sepsis-associated liver injury. High-mobility group box 1 (HMGB1) translocation participates in the development of acute liver failure. However, little information is available on the association between SphK1 and HMGB1 translocation during...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03255-6
更新日期:2020-12-06 00:00:00
abstract::Mammalian target of rapamycin (mTOR) is involved in insulin resistance (IR) and diabetic retinopathy. In retinal pigment epithelial (RPE) cells, insulin activates the mTOR pathway, inducing hypoxia-inducible factor-1α (HIF-1α) and HIF-dependent transcription in serum-free minimum essential medium Eagle (MEM). Serendip...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.178
更新日期:2014-05-08 00:00:00
abstract::Chromatin conformation plays a key role in regulating gene expression and controlling cell differentiation. However, the whole-genome chromatin conformation changes that occur during leukemia cell differentiation are poorly understood. Here, we characterized the changes in chromatin conformation, histone states, chrom...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0173-6
更新日期:2018-02-08 00:00:00
abstract::Emerging evidence has shown that the PIM serine/threonine kinase family, including PIM1, PIM2 and PIM3, is associated with tumour progression towards metastasis. PIM1, an attractive molecular target, has been identified as a potential prognostic biomarker for haematological and epithelial malignancies. However, to dat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0348-9
更新日期:2018-02-22 00:00:00
abstract::The molecular complexes formed by specific members of the family of CARMA proteins, the CARD domain-containing adapter molecule BCL10 and MALT1 (CBM complex) represent a central hub in regulating activation of the pleiotropic transcription factor NF-κB. Recently, missense mutations in CARMA2sh have been shown to cause...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.51
更新日期:2017-02-23 00:00:00
abstract::Enhanced SNHG1 (small nucleolar RNA host gene 1) expression has been found to play a critical role in the initiation and progression of hepatocellular carcinoma (HCC) with its detailed mechanism largely unknown. In this study, we show that SNHG1 promotes the HCC progression through epigenetically silencing CDKN1A and ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03031-6
更新日期:2020-10-02 00:00:00
abstract::MicroRNAs (miRs) are small noncoding RNAs that negatively regulate gene expression by binding to the three untranslated regions of their target mRNAs. Deregulations of miRs were shown to play pivotal roles in tumorigenesis and progression. Recent research efforts have been devoted to translating these basic discoverie...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2014.270
更新日期:2014-07-17 00:00:00
abstract::A major hallmark of Parkinson's disease (PD) is the degeneration of dopaminergic neurons in the substantia nigra, and the causative mechanism is thought to be the activation of programmed neuronal death. Necroptosis is a regulated process of cell death triggered by RIPK1. Although the pathophysiology of PD has been st...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1809-5
更新日期:2019-08-05 00:00:00
abstract::MEIS2 has an important role in development and organogenesis, and is implicated in the pathogenesis of human cancer. The molecular basis of MEIS2 action in tumorigenesis is not clear. Here, we show that MEIS2 is highly expressed in human neuroblastoma cell lines and is required for neuroblastoma cell survival and prol...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.370
更新日期:2014-09-11 00:00:00
abstract::Urethral hypoplasia, including failure of urethral tube closure, is one of the common phenotypes observed in hereditary human disorders, the mechanism of which remains unclear. The present study was thus designed to study the expression, functions, and related mechanisms of the LIM homeobox transcription factor Isl1 t...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1952-z
更新日期:2019-09-26 00:00:00
abstract::Cancer-associated fibroblasts (CAFs) support tumorigenesis by stimulating cancer cell proliferation, and invasion, but how the premalignant stromal fibroblasts trigger epithelial changes remain unclear. We demonstrate that atypical ductal hyperplasia-associated fibroblasts (AHFs) are one kind of activated fibroblasts ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0133-1
更新日期:2018-01-26 00:00:00
abstract::Plastic phenotype convention between glioma stem cells (GSCs) and non-stem tumor cells (NSTCs) significantly fuels glioblastoma heterogeneity that causes therapeutic failure. Recent progressions indicate that glucose metabolic reprogramming could drive cell fates. However, the metabolic pattern of GSCs and NSTCs and i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1015-x
更新日期:2018-09-24 00:00:00
abstract::Bladder cancer (BCa) is the one of the most common cancers with high incidence, occurrence and low 5-year survival rate. Emerging evidence indicates that DLK1-DIO3 genomic region especially the miRNA cluster in this region is involved in several pathologic processes and various cancers, and miR-323a-3p is a member of ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.331
更新日期:2017-08-24 00:00:00
abstract::Liver cancer is the second most common cause of cancer-related death worldwide. Approximately 70-90% of primary liver cancers are hepatocellular carcinoma (HCC). Currently, HCC patient prognosis is unsatisfactory due to high metastasis and/or post-surgical recurrence rates. Therefore, new therapeutic methods for inhib...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0534-9
更新日期:2018-05-01 00:00:00
abstract::Lipid rafts and mitochondria are promising targets in cancer therapy. The synthetic antitumor alkyl-lysophospholipid analog edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) has been reported to target lipid rafts. Here, we have found that edelfosine induced loss of mitochondrial membrane potential an...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.41
更新日期:2011-05-19 00:00:00
abstract::It has been recognized that myocardial apoptosis is one major factor in the development of heart dysfunction and autophagy has been shown to influence the apoptosis. In previous studies, we reported that anti-β1-adrenergic receptor autoantibodies (β1-AABs) decreased myocardial autophagy, but the role of decreased auto...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0445-9
更新日期:2018-03-14 00:00:00
abstract::Epidemiological studies show obvious gender differences in the incidence and the prognosis of bladder cancer (BCa). Estrogen receptor alpha (ERα) was recently shown to play a protective role in BCa. However, the mechanisms by which ERα mediates BCa progression need to be further elucidated. In the present study, we ex...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1827-3
更新日期:2019-08-27 00:00:00
abstract::Mesenchymal stem cells (MSCs) are a heterogeneous population of cells that proliferate in vitro as plastic-adherent cells, have a fibroblast-like morphology, form colonies in vitro and can differentiate into bone, cartilage and fat cells. The abundance, ease and repeatable access to subcutaneous adipose tissue and the...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.344
更新日期:2014-08-21 00:00:00
abstract::Epithelial homeostasis plays an essential role in maintaining endometrial function. But the epithelial role in endometrial fibrosis has been less studied. Previously, we showed that ectopic expression of ΔNp63α is associated with fibrosis process and epithelial dysfunction in endometria of patients with intrauterine a...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2666-y
更新日期:2020-06-11 00:00:00
abstract::Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells are able to deeply influence neuronal chloride homeostasis, by depolarizing the reversal potential of γ-aminobu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.437
更新日期:2014-10-30 00:00:00
abstract::Glucocorticoids (GCs) represent an important component of modern treatment regimens for fludarabine-refractory or TP53-defective chronic lymphocytic leukemia (CLL). However, GC therapy is not effective in all patients. The molecular mechanisms responsible for GC-induced apoptosis and resistance were therefore investig...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.102
更新日期:2012-08-16 00:00:00
abstract::B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) is a member of the Bcl-2 protein family having a pivotal role in triggering cell commitment to apoptosis. Bax is latent and monomeric in the cytosol but transforms into its lethal, mitochondria-embedded oligomeric form in response to cell stress, leading to the rele...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.210
更新日期:2013-06-20 00:00:00
abstract::The glutamate-induced excitotoxicity pathway has been reported in several neurodegenerative diseases. Molecules that inhibit the release of glutamate or cause the overactivation of glutamate receptors can minimize neuronal cell death in these diseases. Osmotin, a homolog of mammalian adiponectin, is a plant protein fr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.538
更新日期:2014-01-30 00:00:00
abstract::The ubiquitin-proteasome system (UPS) and macroautophagy (autophagy) are central to normal proteostasis and interdependent in that autophagy is known to compensate for the UPS to alleviate ensuing proteotoxic stress that impairs cell function. UPS and autophagy dysfunctions are believed to have a major role in the pat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.443
更新日期:2017-01-05 00:00:00
abstract::Alzheimer's Disease (AD) is the most common neurodegenerative disorder in the elderly. Beta-amyloid (Aβ) peptide accumulation is considered as a primary cause of AD pathogenesis, with defective autophagy in patients' brains. Enhanced autophagic activity has been reported to promote Aβ clearance in vitro and in vivo mo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1786-8
更新日期:2019-07-22 00:00:00