Abstract:
:Small-cell lung cancer (SCLC) is an aggressive, rapidly metastasizing neoplasm. The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) is constitutively secreted by marrow stromal cells and plays a key role for homing of hematopoietic cells to the marrow. Here, we report that tumor cells from patients with SCLC express high levels of functional CXCR4 receptors for the chemokine CXCL12. Reverse transcriptase-polymerase chain reaction and flow cytometry demonstrated CXCR4 mRNA and CXCR4 surface expression in SCLC cell lines. Immunohistochemistry of primary tumor samples from SCLC patients revealed high expression of CXCR4. CXCL12 elicited CXCR4 receptor endocytosis, actin polymerization, and a robust activation of phospho-p44/42 mitogen-activated protein kinase in SCLC cells. Furthermore, CXCL12 induced SCLC cell invasion into extracellular matrix and firm adhesion to marrow stromal cells. Stromal cell adhesion of SCLC cells was significantly inhibited by the specific CXCR4 antagonist T140, pertussis toxin, antivascular cell adhesion molecule-1(VCAM-1) antibodies, and CS-1 peptide, demonstrating the importance of CXCR4 chemokine receptor activation and alpha4beta1 integrin binding, respectively. In addition, CXCL12 enhanced the adhesion of SCLC cells to immobilized VCAM-1, demonstrating that CXCR4 chemokine receptors can induce integrin activation on SCLC cells. As SCLC has a high propensity for bone marrow involvement, our findings suggest that CXCR4 chemokine receptors and alpha4beta1 integrins play a critical role in the interaction of SCLC cells with stromal cells in the tumor microenvironment.
journal_name
Oncogenejournal_title
Oncogeneauthors
Burger M,Glodek A,Hartmann T,Schmitt-Gräff A,Silberstein LE,Fujii N,Kipps TJ,Burger JAdoi
10.1038/sj.onc.1207097subject
Has Abstractpub_date
2003-11-06 00:00:00pages
8093-101issue
50eissn
0950-9232issn
1476-5594pii
1207097journal_volume
22pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::A cDNA encoding a complete human c-fos protein was isolated and inserted into two different murine MoMuLV-derived recombinant retroviruses allowing expression of c-fos protein in different cell types. One c-fos-expressing retrovirus, chosen for its ability to express high levels of proteins in fibroblast-like cells, w...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::Epithelial-to-mesenchymal transition (EMT) causes fibrosis, cancer progression and metastasis. Integrin-linked kinase (ILK) is a focal adhesion adaptor and a serine/threonine protein kinase that regulates cell proliferation, survival and EMT. Elucidating the molecular mechanisms necessary for development and progressi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.30
更新日期:2013-01-03 00:00:00
abstract::The phosphatidylinositol 3-kinase (PI3K)/AKT and RAS oncogenic signalling modules are frequently mutated in sporadic human cancer. Although each of these pathways has been shown to play critical roles in driving tumour growth and proliferation, their activation in normal human cells can also promote cell senescence. A...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.394
更新日期:2012-04-12 00:00:00
abstract::Experimental studies performed prior to 1990 led to the widely held belief that matrix metalloproteinases (MMPs) produced by cancer cells are of critical importance in tumor invasion and metastasis. Based on this evidence, the pharmaceutical industry produced several well tolerated, orally active MMP inhibitors (MMPIs...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1204097
更新日期:2000-12-27 00:00:00
abstract::The human c-rel gene (REL), encoding an NF-kappaB transcription factor, is amplified or mutated in several human B-cell lymphomas and can transform chicken lymphoid cells in vitro. We have previously shown that certain deletions of C-terminal transactivation sequences enhance REL's transforming ability in chicken sple...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208902
更新日期:2005-11-10 00:00:00
abstract::In previous studies we changed five conserved amino acid residues in the catalytic domain of the yeast Ras-specific guanine nucleotide exchange factor CDC25GEF (Park et al., 1994). One of the substitutions (R1489E) resulted in a molecule which could bind Ras but was catalytically inactive. These observations suggested...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1200893
更新日期:1997-02-20 00:00:00
abstract::Previous work has demonstrated that E2F proteins regulate the expression of various genes encoding proteins essential for DNA replication and cell-cycle progression. E2F1 in particular is required for the initial entry to the cell cycle from a quiescent state and is required for the activation of other E2F genes. Othe...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.55
更新日期:2008-07-10 00:00:00
abstract::We describe the cytogenetic and molecular characterization of a t(1;13)(q22;q12) constitutional rearrangement occurring in a patient with a relatively benign form of neuroblastoma, called ganglioneuroblastoma. Somatic cell hybrids were generated between mouse 3T3 cells and a lymphoblastoid cell line from this patient,...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract::Dlk/ZIP kinase is a newly discovered serine/threonine kinase which, due to its homology to DAP kinase, was named DAP like kinase, Dlk. This kinase is tightly associated with nuclear structures, it undergoes extensive autophosphorylation and phosphorylates myosin light chain and core histones H3, H2A and H4 in vitro. M...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203170
更新日期:1999-12-02 00:00:00
abstract::The etiology of cancers appears to be complex and multifactorial. Peyton Rous and others demonstrated the process of co-carcinogenesis by exposing rabbits to a virus and tars. Epidemiologists have proposed virus-chemical interactions to cause several cancers. For example, one might propose that the etiology of cervica...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1207822
更新日期:2004-08-23 00:00:00
abstract::The p53 gene has been implicated as a tumor suppressor gene with mutations found in common human cancers. We examined 51 early stage, primary, resected non-small cell lung cancer specimens using an RNAase protection assay and cDNA sequencing. Mutations changing the p53 coding sequence were found in 23/51 (45%) tumor s...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
abstract::The genetic instability driving tumorigenesis is fueled by DNA damage and by errors made by the DNA replication. Upon DNA damage the cell organizes an integrated response not only by the classical DNA repair mechanisms but also involving mechanisms of replication, transcription, chromatin structure dynamics, cell cycl...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208570
更新日期:2005-06-09 00:00:00
abstract::Interferon (IFN)-beta induces S-phase slowing and apoptosis in human papilloma virus (HPV)-positive cervical carcinoma cell line ME-180. Here, we show that apoptosis is a consequence of the S-phase lengthening imposed by IFN-beta, demonstrating the functional correlation between S-phase alteration and apoptosis induct...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208403
更新日期:2005-04-07 00:00:00
abstract::VEGFR-1 (Flt-1), VEGFR-2 (KDR) and VEGFR-3 (Flt4) are endothelial specific receptor tyrosine kinases, regulated by members of the vascular endothelial growth factor family. VEGFRs are indispensable for embryonic vascular development, and are involved in the regulation of many aspects of physiological and pathological ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1203855
更新日期:2000-11-20 00:00:00
abstract::Amplification of HER-2 oncogene was analysed in DNAs obtained from 291 primary human mammary carcinomas. 52/291 (18%) were found to contain amplified HER-2 oncogene. Moderate amplification (2- to 5-fold) was noted in 36/291 (12%). Thirteen tumors (4.5%) had a copy number of 5 to 10. A 10- to 20-fold and greater than 2...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::p73 encodes multiple functionally distinct isoforms. Proapoptotic TAp73 isoforms contain a transactivation (TA) domain, and like p53, have tumor suppressor properties and are activated by chemotherapies to induce cell death. In contrast, antiapoptotic DeltaNp73 isoforms lack the TA domain and are dominant-negative inh...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.59
更新日期:2009-05-14 00:00:00
abstract::Adenomatous polyposis coli (APC) gene mutations have been implicated in familial and sporadic gastrointestinal (GI) cancers. APC mutations are associated with autosomal dominant inheritance of disease in humans. Similarly, mice that contain a single mutant APC gene encoding a protein truncated at residue 716 (Apc(Δ716...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.633
更新日期:2011-06-09 00:00:00
abstract::beta-Catenin, a component of the Wnt signaling pathway, is a coactivator of human androgen receptor (hAR) transcriptional activity. Here, we show that Wnt signaling also influences androgen-mediated signaling through its ability to regulate hAR mRNA and protein in prostate cancer (PCa) cells. Three functional LEF-1/TC...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209366
更新日期:2006-06-08 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) has pivotal roles during embryonic development and carcinoma progression. Members of the Snai1 family of zinc finger transcription factors are central mediators of EMT and induce EMT in part by directly repressing epithelial markers such as E-cadherin, a gatekeeper of the epithe...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.234
更新日期:2010-09-02 00:00:00
abstract::Cyclooxygenase-2 (COX-2) is involved in diverse processes such as inflammation, carcinogenesis and apoptosis. As COX-2 inhibitors interfere with these processes, inhibition of COX-2 has been suggested as a promising anticancer treatment. However, the role of COX-2 in modulation of apoptosis as well as the death pathwa...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206837
更新日期:2003-09-11 00:00:00
abstract::Chromosomal translocation t(X;14)(q28;q11) has been observed in patients with pro-lymphocytic T-cell leukaemia (T-PLL). In two cases of T-PLL, one of which was associated with Ataxia telangiectasia (AT), the chromosomal break occurred in two different introns of a gene c6.1A, located at the Xq28 locus. Fusion transcri...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-12-01 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::Brahma (BRM) is a novel anticancer gene, which is frequently inactivated in a variety of tumor types. Unlike many anticancer genes, BRM is not mutated, but rather epigenetically silenced. In addition, histone deacetylase complex (HDAC) inhibitors are known to reverse BRM silencing, but they also inactivate it via acet...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.613
更新日期:2014-01-30 00:00:00
abstract::Growth arrest after u.v. damage was investigated in C3H mouse primary cultured hepatocytes, spontaneously immortalized liver epithelial cells and their H-ras-transformed derivatives. All cells except for one of the transformed lines had the wild type p53 gene considered necessary for the G1-S checkpoint. Growth arrest...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::MicroRNAs (miRNAs) have been shown to have an important role in various cellular processes, such as apoptosis, differentiation and development. Recent studies have shown that miRNAs are mis-expressed in human cancers where they can exert their effect as oncogenes or tumor suppressors. Here, we review the potential for...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2009.353
更新日期:2008-12-01 00:00:00
abstract::The cellular transcription factor Brn-3a differentially regulates different human papilloma virus (HPV)-16 variants that are associated with different risks of progression to cervical carcinoma in infected humans. The upstream regulatory regions (URRs) of high- and intermediate-risk HPV-16 variants are activated by th...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.33
更新日期:2010-05-06 00:00:00
abstract::Although established cell lines can be transformed with oncogenic ras, primary epithelial cells cannot, but require the coexpression of an immortalizing oncogene, such as the E1A region of adenovirus. We have previously shown that immortalization of primary epithelial cells by E1A 12S requires the expression of five r...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-12-19 00:00:00
abstract::Defining apoptosis-regulatory cascades of the epithelium is important for understanding carcinogenesis, since cancer cells are considered to arise as a result of the collapse of the cascades. We previously reported that a novel gene GASDERMIN (GSDM) is expressed in the stomach but suppressed in gastric cancer cell lin...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210475
更新日期:2007-10-04 00:00:00
abstract::Overexpressed or activated hepatocyte growth factor receptor, encoded by the MET proto-oncogene, was found in the majority of colorectal carcinomas (CRCs), whose stepwise progression to malignancy requires transcriptional activation of beta-catenin. We here demonstrate that a functional crosstalk between Met and beta-...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209859
更新日期:2007-02-15 00:00:00
abstract::Elucidation of mechanisms underlying the increased androgen receptor (AR) activity and subsequent development of aggressive prostate cancer (PrCa) is pivotal in developing new therapies. Using a systems biology approach, we interrogated the AR-regulated proteome and identified PDZ binding kinase (PBK) as a novel AR-re...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0501-z
更新日期:2019-02-01 00:00:00