Abstract：
:Hypoxia drives malignant progression in part by promoting accumulation of the oncogenic transcription factor hypoxia inducible factor-1α (HIF-1α) in tumor cells. Tumor aggressiveness also relates to elevation of the cancer stem cell-associated membrane protein CD24, which has been causally implicated in tumor formation and metastasis in experimental models. Here, we link these two elements by showing that hypoxia induces CD24 expression through a functional hypoxia responsive element in the CD24 promoter. HIF-1α overexpression induced CD24 mRNA and protein under normoxic conditions, with this effect traced to a recruitment of endogenous HIF-1α to the CD24 promoter. Short hairpin RNA-mediated attenuation of HIF-1α or CD24 expression reduced cancer cell survival in vitro and in vivo at the levels of primary and metastatic tumor growth. CD24 overexpression in HIF-1α-depleted cancer cells rescued this decrease, whereas HIF-1α overexpression in CD24-depleted cells did not. Analysis of clinical tumor specimens revealed a correlation between HIF-1α and CD24 levels and an association of their coexpression to decreased patient survival. Our results establish a mechanistic linkage between 2 critically important molecules in cancer, identifying CD24 as a critical HIF-1α transcriptional target and biologic effector, strengthening the rationale to target CD24 for cancer therapy.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Thomas S,Harding MA,Smith SC,Overdevest JB,Nitz MD,Frierson HF,Tomlins SA,Kristiansen G,Theodorescu Ddoi
10.1158/0008-5472.CAN-11-3666subject
Has Abstractpub_date
2012-11-01 00:00:00pages
5600-12issue
21eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-11-3666journal_volume
72pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Histone deacetylase (HDAC) inhibitors are known to exert antimetastatic and antiangiogenic activity in vitro and in vivo. RECK is a membrane-anchored glycoprotein that negatively regulates matrix metalloproteinases (MMPs) and inhibits tumor metastasis and angiogenesis. In this study, we test the possibility that HDAC ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-06-15 00:00:00
abstract：:Expression of the c-Myc oncoprotein is affected by conserved threonine 58 (T58) and serine 62 (S62) phosphorylation sites that help to regulate c-Myc protein stability, and altered ratios of T58 and S62 phosphorylation have been observed in human cancer. Here, we report the development of 3 unique c-myc knock-in mice ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-1032
更新日期：2011-02-01 00:00:00
abstract：:A cell line derived from early passage of a transplantable tumor in athymic mice that initially had been injected with human breast adenocarcinoma cells produced a substantial amount of RNA sequences related to the Kirsten murine leukemia virus. The cell line derived from later passage of transplantation of these tumo...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-08-01 00:00:00
abstract：:Chronic exposure to the hepatocellular carcinogen diethylnitrosamine (DEN) causes a dose-dependent accumulation of the promutagenic DNA adduct O4-ethyldeoxythymidine in hepatocytes and increases in the number of initiated hepatocytes as indicated by gamma-glutamyl transpeptidase positive foci. Initiation is thought to...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-12-15 00:00:00
abstract：:Sera from 91 adult acute nonlymphocytic leukemia patients were tested for circulating immune complexes by the C1q binding test. In 42 patients tested prior to the initiation of therapy, C1q binding activity was inversely correlated with leukemic infiltrate of the bone marrow (rs = -0.34, p less than 0.02), but it was ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-07-01 00:00:00
abstract：:The expression of 8 oncogenes and the structures of 19 oncogenes were analyzed in 15 adenocarcinomas (12 primary and 3 metastatic), 18 adenomatous polyps, and 18 normal colonic mucosae derived from 19 patients with familial polyposis coli. The expression of c-myc gene was most elevated in carcinoma, and moderately ele...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-09-01 00:00:00
abstract：:High-grade gliomas are characterized by exuberant vascularization, diffuse invasion, and significant chemoresistance, resulting in a recurrent phenotype that makes them impossible to eradicate in the long term. Targeting protumoral signals in the glioma microenvironment could have significant impact against tumor cell...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-0685
更新日期：2014-10-01 00:00:00
abstract：:Cancer in a host induces responses that increase the ability of the microenvironment to sustain the growing mass, for example, angiogenesis, but cancer cells can have varying sensitivities to these sustainability signals. Here, we show that these sensitivities are significant determinants of ultimate tumor fate, espec...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-12-4590
更新日期：2013-06-15 00:00:00
abstract：:It has been proposed that occult, disseminated metastatic cells are refractory to chemotherapy due to lack of proliferation. We have shown that p38 activation induces dormancy of squamous carcinoma cells. We now show that p38 signaling in these cells activates a prosurvival mechanism via the up-regulation of the endop...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-3092
更新日期：2006-02-01 00:00:00
abstract：:Class I major histocompatibility complex (MHC) antigen expression in neuroblastoma may play a role in the oncogenicity of this embryonal tumor of childhood. Since N-myc amplification in neuroblastoma tumors is associated with rapid tumor progression (33) and N-myc decreases Class I MHC antigen expression in rat neurob...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-06-15 00:00:00
abstract：:The effects of the anthracycline antiboties, daunomycin and adriamycin, on the DNA-directed activities of DNA polymerases from murine sarcoma virus, rat liver (high-molecular-weight species), Escherichia coli, and Micrococcus luteus were determined. Under all conditions tested, these compounds had greater inhibitory e...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-03-01 00:00:00
abstract：:Triple-negative breast cancers (TNBC) are highly aggressive, lack FDA-approved targeted therapies, and frequently recur, making the discovery of novel therapeutic targets for this disease imperative. Our previous analysis of the molecular mechanisms of action of bromodomain and extraterminal protein inhibitors (BETi) ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-1571
更新日期：2017-10-01 00:00:00
abstract：:The ability to modulate DNA repair has been proposed as an effective method to overcome cytotoxic drug resistance in human tumors. However, no studies have shown that it is possible to achieve modulation of DNA repair in humans in vivo. This study analyzes modulation of O6-alkylguanine-DNA alkyltransferase, a DNA repa...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-06-01 00:00:00
abstract：:More than 500 colorectal tumors with clonal chromosomal abnormalities have been reported. Although the pattern of aberrations is nonrandom, no specific primary or secondary karyotypic abnormality has been identified. Also, the chronological order in which the aberrations appear during disease progression is not well k...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-10-15 00:00:00
abstract：:A consecutive series of 99 untreated patients undergoing radical surgical resection for stage I-IV laryngeal carcinomas has been studied prospectively. Our purpose was to analyze the predictive relevance of proliferative variables studied [proliferating cell nuclear antigen (PCNA) expression, volume-corrected mitotic ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-12-15 00:00:00
abstract：:The multistage process of cancer formation is driven by the progressive acquisition of somatic mutations. Replication stress creates genomic instability in mammals. Using a well-defined multistep leukemia model driven by Spi-1/PU.1 overexpression in the mouse and Spi-1/PU.1-overexpressing human leukemic cells, we inve...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-4691
更新日期：2010-09-01 00:00:00
abstract：:New facets to Knudson's [corrected] "two-hit" hypothesis have been proposed recently in relation to adenomatous polyposis coli (APC): protein inactivation may be selected weakly, and the two hits may be interdependent. We reviewed published data on 165 sporadic and 102 familial adenomatous polyposis-associated colorec...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-01-15 00:00:00
abstract：:Xeroderma pigmentosum (XP) is a sun-sensitive, cancer-prone genetic disorder characterized by a defect in nucleotide excision repair. The human nucleotide excision repair and transcription gene ERCC2 is able to restore survival to normal levels after exposure to UV light in XP complementation group D cells. No enhance...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:The effects of 5-mercapto-2'-deoxyuridine (MUdr) on DNA synthesis in a primary murine spleen lymphocyte culture system stimulated by phytohemagglutinin (PHA) were studied. Inhibition of thymidine incorporation into acid insoluble nucleic acid material was 50% at 0.5 mM MUdR concentration, while inhibition of deoxyurid...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-09-01 00:00:00
abstract：:The pharmacokinetics of vinblastine in humans was examined using a radioimmunoassay specific for both the Vinca alkaloids and aromatic ring [3H]vinblastine. The data were consistent with a three-compartment open model system with the following values, alpha phase: t1/2=3.90+/-1.46 min; Vc=16.8+/-7.1 liters. beta phase...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-08-01 00:00:00
abstract：:Aluminum sulfonated phthalocyanine has potential as a suitable photosensitizer for use in the photodynamic therapy of cancer. In the present study, cellular uptake and retention of the individual mono-, di-, tri-, and tetrasulfonated derivatives (AlS1-4Pc) were examined in tissue culture and in normal and neoplastic t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-08-01 00:00:00
abstract：:The frequency and mutational profile of H-ras gene activation were determined in spontaneous liver tumors of male C57BL/6 x C3H/He mice and in tumors induced with the genotoxic hepatocarcinogen benzidine.2 HCl or the nongenotoxic hepatocarcinogens phenobarbital, chloroform, and ciprofibrate. DNA sequence analysis of t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
abstract：:Mutations in the adenomatous polyposis coli (APC) gene and K-ras occur in the majority of human colorectal cancers. Loss of functional APC protein activates the Wnt signal transduction pathway, allowing the nuclear accumulation of beta-catenin, which then binds to T-cell factor-4 (Tcf-4), causing increased transcripti...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-02-01 00:00:00
abstract：:Tn and sialylated Tn (sTn) are blood group-related epitopes expressed on mucins of colon carcinoma and other epithelial tumors and are, therefore, potential targets for immunological control. We have immunized 20 colorectal cancer patients at high risk for recurrence with a vaccine consisting of partially desialylated...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-10-15 00:00:00
abstract：:We analyzed the karyotype of 27 B-cell lymphomas of human origin that developed in mice with severe combined immunodeficiency disease following the injection of peripheral blood leukocytes from Epstein-Barr virus-seropositive donors. Three tumors had clonal abnormalities detected with conventional techniques, 2 had tr...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-09-01 00:00:00
abstract：:Tumors often display mechanisms to avoid or suppress immune recognition. One such mechanism is the shedding of gangliosides into the local tumor microenvironment, and a high concentration of circulating gangliosides is associated with poor prognosis. In this study, we identify ganglioside GD3, which was isolated from ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-2695
更新日期：2012-08-01 00:00:00
abstract：:Medulloblastoma (MB) represents the most frequent malignant brain tumor of childhood but only a few cell lines and animal models of this primitive neuroectodermal tumor (PNET) have thus far been established. Using specific cell culture conditions, we were able to derive four human MB cell lines (MHH-MED-1-4) as well a...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-06-15 00:00:00
abstract：:Aberrant methylation of promoter CpG islands (CGI) is involved in silencing of tumor suppressor genes and is also a potential cancer biomarker. Here, to identify CGIs aberrantly methylated in human melanomas, we did a genome-wide search using methylation-sensitive representational difference analysis. CGIs in putative...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-0157
更新日期：2006-06-15 00:00:00
abstract：:Diagnosis of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC), particularly HCC independent of cirrhosis etiology, presents a great challenge because of a lack of biomarkers. Here we test the hypothesis that expression profiles of microRNAs (miRNAs) in serum can serve as biomarkers for diagnosis of HBV ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-1001
更新日期：2010-12-01 00:00:00
abstract：:Ten aminoacyl transfer RNA's prepared from human malignant trophoblastic cells (BeWo line) were compared with the corresponding aminoacyl transfer RNA's from normal human chorionic tissue by cochromatography on a RPC-5 column. Phenylalanyl transfer RNA (Phe-tRNA) of BeWo cells had, in addition to the single species of...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-08-01 00:00:00
