Abstract:
:TGF-β is a multifunctional cytokine affecting many cell types and implicated in tissue remodeling processes. Due to its many functions and cell-specific effects, the consequences of TGF-β signaling are process-and stage-dependent, and it is not uncommon that TGF-β exerts distinct and sometimes opposing effects on a disease progression depending on the stage and on the pathological changes associated with the stage. The mechanisms underlying cell- and process-specific effects of TGF-β are poorly understood. We are describing a novel pathway that mediates induction of angiogenesis in response to TGF-β1. We found that in endothelial cells (EC) thrombospondin-4 (TSP-4), a secreted extracellular matrix (ECM) protein, is upregulated in response to TGF-β1 and mediates the effects of TGF-β1 on angiogenesis. Upregulation of TSP-4 does not require the synthesis of new protein, is not caused by decreased secretion of TSP-4, and is mediated by activation of SMAD3. Using Thbs4-/- mice and TSP-4 shRNA, we found that TSP-4 mediated pro-angiogenic functions in cultured EC and angiogenesis in vivo in response to TGF-β1. We observed~3-fold increases in tumor mass and levels of angiogenesis markers in animals injected with TGF-β1, and these effects did not occur in Thbs4-/- animals. Injections of an inhibitor of TGF-β1 signaling SB-431542 also decreased the weights of tumors and cancer angiogenesis. Our results from in vivo angiogenesis models and cultured EC document that TSP-4 mediates upregulation of angiogenesis by TGF-β1. Upregulation of pro-angiogenic TSP-4 and selective effects of TSP-4 on EC may contribute to stimulation of tumor growth by TGF-β despite the inhibition of cancer cell proliferation.
journal_name
Oncogenejournal_title
Oncogeneauthors
Muppala S,Xiao R,Krukovets I,Verbovetsky D,Yendamuri R,Habib N,Raman P,Plow E,Stenina-Adognravi Odoi
10.1038/onc.2017.140subject
Has Abstractpub_date
2017-09-07 00:00:00pages
5189-5198issue
36eissn
0950-9232issn
1476-5594pii
onc2017140journal_volume
36pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Resistance and relapse are still primary causes that result in poor effectiveness of chemotherapy in malignant gliomas. Therefore, development of new therapeutic strategies requires the identification of key molecular pathways regulating chemoresistance. We previously found that abnormal high expression of the Tie2 re...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.103
更新日期:2009-06-18 00:00:00
abstract::I briefly review the discovery and characterization of the first human retrovirus, human T-cell leukemia virus type 1, focusing on contributions from Japanese researchers. The unique regulatory mechanisms for the viral regulation with Tax and Rex, etiology of ATL and possible leukemogenic mechanism with Tax are also d...
journal_title:Oncogene
pub_type: 历史文章,杂志文章,评审
doi:10.1038/sj.onc.1208981
更新日期:2005-09-05 00:00:00
abstract::Guanine nucleotide exchange factors from the Dbl family are proto-oncogenic proteins that activate small GTPases of the Rho family. Here we report the characterization of GEF720, a novel Dbl-like protein related to p115Rho-GEF. GEF720 activated RhoA both in our recently developed Yeast Exchange Assay and in biochemica...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204921
更新日期:2001-11-01 00:00:00
abstract::The SCL/TAL1 gene was originally identified by virtue of its rearrangement and transcriptional activation in patients with T cell acute lymphoblastic leukaemia. It encodes a helix-loop-helix transcription factor, is not normally expressed in T cells, but is expressed in erythroid, mast, megakaryocytic and progenitor c...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-07-06 00:00:00
abstract::Castration-resistant prostate cancer (CRPC) continues to be a major clinical problem and the mechanisms behind it remain unclear. Thioredoxin domain-containing protein 5 (TXNDC5) is involved in protein folding and chaperone activity, and its overexpression has been reported in multiple malignancies. In the current stu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.401
更新日期:2015-09-03 00:00:00
abstract::Alternative splicing is a widespread process contributing to structural transcript variation and proteome diversity. In cancer, the splicing process is commonly disrupted, resulting in both functional and non-functional end-products. Cancer-specific splicing events are known to contribute to disease progression; howev...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2015.318
更新日期:2016-05-12 00:00:00
abstract::A hallmark of cancer is the deregulation of cell-cycle machinery, ultimately facilitating aberrant proliferation that fuels tumorigenesis and disease progression. Particularly, in breast cancers, cyclin D1 has a crucial role in the development of disease. Recently, a highly specific inhibitor of CDK4/6 activity (PD-03...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.154
更新日期:2010-07-15 00:00:00
abstract::The myc proto-oncogenes are transcription factors that directly regulate the expression of other genes, by binding to the specific DNA sequence, CACGTG. Among the target genes for c-Myc regulation are ECA39, p53, ornithine decarboxylase (ODC), alpha-prothymosin and Cdc25A. In this study we examined the involvement of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201939
更新日期:1998-07-16 00:00:00
abstract::The autosomal dominantly inherited disease tuberous sclerosis (TSC) affects approximately 1 in 6000 individuals and is characterized by the development of tumors, named hamartomas, in different organs. TSC1, encoding hamartin, and TSC2, encoding tuberin are tumor suppressor genes responsible for TSC. Hamartin and tube...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209812
更新日期:2007-01-25 00:00:00
abstract::CCAAT/enhancer-binding protein-δ (C/EBP-δ), a transcription factor, is elevated in carcinoma compared with that in normal tissue. This study reports a novel function of C/EBP-δ in lymphangiogenesis and tumor metastasis. Genetic deletion of C/EBP-δ in mice resulted in a significant reduction of lymphangiogenesis and pu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.187
更新日期:2011-12-08 00:00:00
abstract::Castration-resistant prostate cancer (CRPC) continues to pose a significant clinical challenge with new generation second-line hormonal therapies affording limited improvement in disease outcome. As the androgen receptor (AR) remains a critical driver in CRPC, understanding the determinants of its transcriptional acti...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.508
更新日期:2014-12-11 00:00:00
abstract::Prostate cancer is the second highest cause of cancer-related deaths of men in the US. Signal transducers and activators of transcription (STATs) proteins are a small family of latent cytoplasmic transcription factors that act downstream of Janus kinase (JAK) activation and mediate intracellular signaling from a wide ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208437
更新日期:2005-03-17 00:00:00
abstract::Disseminated breast cancer cells employ adaptive molecular responses following cytotoxic therapeutic insult which promotes their survival and subsequent outgrowth. Here we demonstrate that expression of the pro-metastatic lncRNA BORG (BMP/OP-Responsive Gene) is greatly induced within triple-negative breast cancer (TNB...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0586-4
更新日期:2019-03-01 00:00:00
abstract::The MET oncogene encodes the receptor for HGF/Scatter Factor, known to control cell motility and invasion in epithelial cells. We report that the Met/HGF receptor, absent in differentiated adult skeletal muscles, is aberrantly expressed in clinical samples and in established cell lines of human rhadbomyosarcomas. In b...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-04-18 00:00:00
abstract::The Wilms' Tumor 1 gene (WT1) encodes a transcription factor of the zinc-finger family. As a result of alternative RNA splicing, the gene can be expressed as four polypeptides which differ in the presence or absence of two stretches of amino acids: one of 17 residues (17aa) just N-terminal of the four zinc-fingers and...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::Thymosin beta-4 (Tbeta-4), a small peptide originally isolated from calf thymus, modulates the formation of F-actin microfilaments by sequestering the monomeric G-actin. Recent studies have shown that overexpression of the Tbeta-4 gene occurs not only in many human carcinomas but also in the highly metastatic melanoma...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206404
更新日期:2003-05-22 00:00:00
abstract::Ataxia telangiectasia (AT) is a human hereditary syndrome whose underlying gene product, ataxia telangiectasia mutated (ATM) protein kinase, is involved in multiple intracellular signaling pathways. We demonstrated previously that AT fibroblasts are defective in intracellular Ca(2+) mobilization in response to both st...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206167
更新日期:2003-01-23 00:00:00
abstract::Treatment of fibroblasts with the phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate (TPA), specifically inhibits fibroblast growth factor-2 (FGF-2) induced proliferation. TPA treatment has little or no effect on FGF receptor activation but specifically inhibits the activation of p38 MAPK but not other downstream si...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205268
更新日期:2002-03-27 00:00:00
abstract::Molecular, functional, and clinical analyses strongly suggest that chromosome segment 11p15.5 contains a gene involved in lung cancer pathogenesis. The critical region of allele loss is 310 kb in size. We used our contig of P1-phage artificial chromosome (PAC) clones together with newly identified bacterial artificial...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205027
更新日期:2001-12-06 00:00:00
abstract::Myeloid differentiation is a highly regulated process governed by various cytokines, such as EPO, TPO, G-CSF, IL-3, IL-5 and GM-CSF. These cytokines act in part through activation of the STAT transcription factor family. In particular, various isoforms of STAT3 and STAT5 are activated during myeloid differentiation in...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1203479
更新日期:2000-05-15 00:00:00
abstract::To investigate the mechanisms by which p53 suppresses cell transformation, we used the simian virus 40 (SV40) large T antigen (LTag), the adenovirus E1a proteins, and an activated ras protein (EJ-ras), to examine different pathways of transformation for their susceptibility to suppression by p53: While p53 can suppres...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-12-21 00:00:00
abstract::Gastric carcinogenesis is a multistep process involving genetic and epigenetic alteration of protein-coding proto-oncogenes and tumor-suppressor genes. Recent discoveries have shed new light on the involvement of a class of noncoding RNA known as microRNA (miRNA) in gastric cancer. A substantial number of miRNAs show ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2010.352
更新日期:2010-10-28 00:00:00
abstract::The c-Myc oncoprotein is a basic-helix-loop-helix-leucine zipper (b-HLH-LZ) transcription factor involved in regulating cell proliferation and differentiation. We have used retrovirus-mediated gene transfer to investigate the effect of ectopic c-Myc expression on the spontaneous differentiation of primary quail myobla...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::The retinoblastoma (Rb) tumor suppressor gene and its close relatives p107 and p130 are best known for their function in the control of cell cycle progression. In recent years, however, a new role for these proteins has been emerging as they have been linked with regulation of terminal differentiation of many tissues ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1203244
更新日期:1999-12-20 00:00:00
abstract::We have previously shown that the death receptor ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) induces an increase of intracellular C(16)-ceramide in sensitive SW480 but not in resistant SW620 cells. Resistance in SW620 cells was overcome by exogenous ceramide, leading us to propose that defec...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.468
更新日期:2009-02-26 00:00:00
abstract::We present an approach making use of technology established in the context of the genome project to describe a pancreatic cancer-specific expression profile and to identify new potential disease genes or disease-associated-genes. By use of gridded arrays of pancreatic cancer cDNA libraries and differential hybridizati...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-10-17 00:00:00
abstract::Hexokinase-II (HK2) is a key enzyme involved in glycolysis, which is required for breast cancer progression. However, the underlying post-translational mechanisms of HK2 activity are poorly understood. Here, we showed that Proviral Insertion in Murine Lymphomas 2 (PIM2) directly bound to HK2 and phosphorylated HK2 on ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0386-x
更新日期:2018-11-01 00:00:00
abstract::We have utilized c-abl antibodies and an in vitro kinase assay to identify the protein products of the c-abl gene in mouse testis. Although the testis contains high levels of a unique c-abl mRNA, along with lower amounts of two c-abl mRNAs common to somatic cells, we detected only a single polypeptide of approximately...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1989-06-01 00:00:00
abstract::Bone metastatic prostate cancer provokes extensive osteogenesis by driving the recruitment and osteoblastic differentiation of mesenchymal stromal cells (MSCs). The resulting lesions greatly contribute to patient morbidity and mortality, underscoring the need for defining how prostate metastases subvert the MSC-osteob...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0913-4
更新日期:2019-10-01 00:00:00
abstract::The epidermis is continually exposed to harmful mutagens that have the potential to cause DNA damage. To protect the skin from accumulating mutated cells, keratinocytes have developed a highly regulated mechanism of eliminating damaged cells through apoptosis. Bcl-xL is a well-described cell survival protein that when...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202836
更新日期:1999-08-05 00:00:00