Abstract:
:Both Pten and Nras are downstream mediators of receptor tyrosine kinase activation that plays important roles in controlling cell survival and proliferation. Here, we investigated whether and how Pten loss cross-talks with Nras activation in driving liver cancer development in mice. Somatic disruption of hepatic Pten and overexpression of Nras were achieved in out-bred immunocompetent CD-1 mice through a hydrodynamic delivery of plasmids carrying Sleeping Beauty transposon-based integration of Nras and the CRISPR/Cas9-mediated Pten knockout system. Concurrent Pten knockout and Nras knock-in induced hepatocellular carcinoma, while individual gene manipulation failed. Tumor development was associated with liver fibrosis, hyperlipidemia, hepatic deposition of lipid droplets and glycogen, and hepatomegaly. At the molecular level, lipid droplet formation was primarily contributed by upregulated expression of genes responsible for lipogenesis and fatty acid sequestration, such as Srebpf1, Acc, Pparg and its downstream targets. Our findings demonstrated that Pten disruption was synergized by Nras overexpression in driving hepatocyte malignant transformation, which correlated with extensive formation of lipid droplets.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Gao M,Liu Ddoi
10.1080/15384047.2017.1323597subject
Has Abstractpub_date
2017-07-03 00:00:00pages
505-512issue
7eissn
1538-4047issn
1555-8576journal_volume
18pub_type
杂志文章abstract::Onconase (Onc), a ribonuclease from oocytes or early embryos of Northern Leopard frog (Rana pipiens), is cytostatic and cytotoxic to a variety of tumor lines in vitro, inhibits growth of tumors in animal in vivo models and is currently in Phase IIIb clinical trials for malignant mesothelioma where it displays antitumo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.7.6172
更新日期:2008-07-01 00:00:00
abstract::Multidrug resistance (MDR) is an important cause of treatment failure in acute lymphoblastic leukemia (ALL). The ABC family of membrane transporters is proposed, albeit with controversy, to be involved in this process. The present study aims to investigate the mRNA expression profile of several genes of this family, i...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.26603
更新日期:2014-01-01 00:00:00
abstract::Arsenic trioxide (As2O3) induces apoptosis in certain types of cancer cells. But the detailed mechanisms of As2O3 efficacy are not completely known. Here we demonstrate that As2O3 has a therapeutic effect on cervical cancer in vitro and in vivo. We investigated the As2O3-induced apoptosis in various cervical cancer ce...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.4.3887
更新日期:2007-04-01 00:00:00
abstract:PURPOSE:The pelvic failure rate decreases with increase in the radiation dose but the complications increase. The four field pelvic technique has a theoretical advantage of providing a higher tumor dose with less dose to the surrounding normal tissue thus reducing the complications. RESULT:Eighty-three patients comple...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,随机对照试验
doi:10.4161/cbt.8.9.8129
更新日期:2009-05-01 00:00:00
abstract::Antivascular therapy provides a promising method for anticancer therapy. But targeting to gastric cancer vessels is nonselective due in part to the lack of specific cell-surface receptors identified on target vascular cells. Herein we used in vivo screening of phage displayed peptide library to identify some peptides ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.12.1223
更新日期:2004-12-01 00:00:00
abstract::B-cell chronic lymphocytic leukemia (CLL) is caused by the abnormal accumulation of non-functional B-cells in peripheral blood and bone marrow. However, the precise aetiology and mechanism of the disease are unclear. Recently, progress has been made in the identification of both the genetic deficiencies and environmen...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.7.2.5262
更新日期:2008-02-01 00:00:00
abstract::Mcl-1, a pro-survival member of the Bcl-2 protein family, is an attractive target for cancer therapy. We have recently identified the natural product marinopyrrole A (maritoclax) as a novel small molecule Mcl-1 inhibitor. Here, we describe the structure-activity relationship study of pyoluteorin derivatives based on m...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/15384047.2014.972799
更新日期:2014-01-01 00:00:00
abstract::Aggressive fibromatosis (AF) or desmoid tumors is an aggressive fibroblastic proliferation which is locally invasive but can not metastasize. The treatment of AF is challenging. Surgery was the main treatment modality for AF in the past, other strategies including radiotherapy, systemic therapies and wait-and-see poli...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1373215
更新日期:2017-10-03 00:00:00
abstract::The pediatric solid tumor neuroblastoma (NB) often depends on the anti-apoptotic protein, Mcl(-)1, for survival through Mcl(-)1 sequestration of pro-apoptotic Bim. High affinity Mcl(-)1 inhibitors currently do not exist such that novel methods to inhibit Mcl(-)1 clinically are in high demand. Receptor tyrosine kinases...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2014.1002333
更新日期:2015-01-01 00:00:00
abstract::Double-strand breaks are one the most severe types of DNA damage with respect to cell survival and the preservation of genomic integrity. Therefore, cells have evolved complex mechanisms including cell cycle regulation, activation of repair pathways and in certain cases induction of apoptosis in response to these lesi...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.3.7.917
更新日期:2004-07-01 00:00:00
abstract::We investigated the expression of annexin-1 (ANXA1) in thyroid carcinoma cell lines and in thyroid cancers with a different degree of differentiation. The highest level of ANXA1 expression examined by Western blotting was detected in the papillary carcinoma cells (NPA) and in the follicular cells (WRO). On the other h...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.6.2700
更新日期:2006-06-01 00:00:00
abstract::The androgen receptor is one of the central factors in mediating prostate cancer progression and is an important target for treatment. Several possible mechanisms have been put forth as to how it promotes this process. In the January 2004 issue of Nature Medicine, Chen et al. report that the androgen receptor is consi...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.3.785
更新日期:2004-03-01 00:00:00
abstract::RNA-dependent protein kinase is an interferon-induced, double-stranded (ds), RNA-activated serine/threonine protein kinase involved in the eukaryotic response to viral infection. While PKR also functions in cellular differentiation, growth control and apoptosis, its role in human cancer remains poorly understood. To e...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.3.7386
更新日期:2009-02-01 00:00:00
abstract:OBJECTIVES:Chemotherapy-induced diarrhea (CID) is a well recognized side effect of cancer treatment. However, the pathophysiology behind this debilitating side effect remains unclear. Irinotecan causes cholinergic and delayed onset diarrhea in patients, in which beta-glucuronidase produced by gut bacteria is thought to...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.12.6940
更新日期:2008-12-01 00:00:00
abstract::Antitumor imidazoacridinone C-1311 is a DNA-reactive topoisomerase II and FLT3 receptor tyrosine kinase inhibitor. Here, we demonstrate the mechanism of C-1311 inhibitory action on novel targets: hypoxia-inducible factor-1α (HIF-1α), vascular-endothelial growth factor (VEGF), and angiogenesis. In a cell-free system, C...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.7.15980
更新日期:2011-10-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is a critical early event in tumorigenesis. The contribution of heparan sulfate (HS) to EMT has not been fully elucidated. HS D-glucosaminyl 3-O-sulfotransferase-3B1 (3-OST-3B1) participates in the final step of HS fine structure biosynthesis, whose involvement in cancer has yet...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.5.15957
更新日期:2011-09-01 00:00:00
abstract::Head and neck squamous cell carcinoma (HNSCC) remains a significant cause of morbidity and mortality. There has been a great interest in finding specific genomic changes which contribute to HNSCC tumorigenesis, especially within the chromosome 3p area, where high frequency of LOH (loss of heterozygosity) has been repo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.7.12886
更新日期:2010-10-01 00:00:00
abstract::Understanding molecular mechanisms involved in melanoma resistance to drugs is a big challenge. Experimental evidences suggested a correlation between mutational status in B-RAF and melanoma cell susceptibility to drugs, such as paclitaxel, doxorubicin and temozolomide, which generate an accumulation of hydrogen perox...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1030546
更新日期:2015-01-01 00:00:00
abstract::Long standing chronic pancreatitis is a risk factor for developing pancreatic cancer. Inheritance of polymorphisms in SPINK1 and CFTR are associated with an increased risk of developing pancreatitis. The aim of this study was to determine if patients who carry polymorphisms in SPINK1 and CFTR are at increased risk of ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:
更新日期:2003-11-01 00:00:00
abstract::The Chemohormonal Therapy vs Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) was a randomized phase III trial that evaluated the outcomes of men with metastatic prostate cancer who received castration with or without docetaxel. Patients from this trial were genotyped in a recent ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1796195
更新日期:2020-09-01 00:00:00
abstract::Epigenetics are defined, in broad-terms, as alterations in gene expression without changes in DNA sequence. While histone modifications and DNA methylation are two classical means to regulate gene expression, miRNA has also recently been documented to govern gene expression in normal as well as cancer cells. In this r...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.7.9.6992
更新日期:2008-09-01 00:00:00
abstract::Resistance to apoptosis is one reason for the poor response of malignant brain tumors to therapy. The PPARgamma-modulating drug Troglitazone downregulates the anti-apoptotic FLIP protein and sensitizes glioblastoma cells to apoptosis induced by the death ligand TRAIL. To investigate the molecular basis of an experimen...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.12.6966
更新日期:2008-12-01 00:00:00
abstract::The early observations by Dr Otto Warburg revealed that fundamentally metabolic differences exist between malignant tumor cells and adjacent normal cells. Many studies have further reported the relationship between altered cellular metabolism and therapeutic outcomes. These observations suggest that targeting the pecu...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.22958
更新日期:2013-02-01 00:00:00
abstract::Activation of MAP kinases is involved in various cellular processes, including immunoregulation, inflammation, cell growth, cell differentiation, and cell death. To investigate the role of p38 MAP kinase activation in the signaling pathway of TRAIL-mediated apoptosis, we compared TRAIL-mediated MAP kinase activation i...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.3.696
更新日期:2004-03-01 00:00:00
abstract::Invariant natural killer T (iNKT) cells are a distinct subset of human T cells, which expresses an invariant T cell receptor Vα24 Jα18 and recognizes glycolipid antigens in the context of CD1d molecules. iNKT cells exert pivotal regulatory roles in many immune responses, including antitumor immune responses. Alteratio...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.20553
更新日期:2012-07-01 00:00:00
abstract::Current treatment modalities for pancreatic carcinoma afford only modest survival benefits. TRAIL, as a potent and specific inducer of apoptosis in cancer cells, would be a promising new treatment option. However, since not all pancreatic cancer cells respond to TRAIL, further improvements and optimizations are still ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/15384047.2014.972183
更新日期:2014-01-01 00:00:00
abstract:OBJECTIVES:The biochemical response of prostatic cells to needle core biopsies is known to manifest as a rise in serum PSA. The aim of this study is to evaluate the PSA response to mechanical trauma in prostate cancer patients, when compared to benign controls. MATERIALS AND METHODS:50 consecutive patients undergoing ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.181
更新日期:2003-01-01 00:00:00
abstract::Multiple myeloma (MM) is an incurable B-cell malignancy characterized by accumulation of malignant plasma cells in the bone marrow and by recurrent or persistent infections. Toll-like receptors (TLRs) are essential in the host defense against infections. The aim of this study was to investigate TLR initiated responses...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.1.13878
更新日期:2011-01-01 00:00:00
abstract::Obesity is considered one of the risk factors for many cancers. Serum leptin levels are often elevated in obese people. Leptin has been reported to act as a mitogenic agent and promote renal cancer cell proliferation, whereas the detailed mechanisms still remain to be elucidated. The purpose of this study is to invest...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.11.6837
更新日期:2008-11-01 00:00:00
abstract::Breast cancers often have deregulated hepatocyte growth factor (HGF) and c-Met signaling that results in increased tumor growth and invasion. Elucidating the mechanism responsible for HGF/c-Met action in breast cancer progression has been difficult as c-Met communicates with a number of secondary receptors that can le...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.4.3851
更新日期:2007-04-01 00:00:00