Abstract:
:In principle, the inhibition of candidate gain-of-function genes defined through genomic analyses of large patient cohorts offers an attractive therapeutic strategy. In this study, we focused on changes in expression of CD24, a well-validated clinical biomarker of poor prognosis and a driver of tumor growth and metastasis, as a benchmark to assess functional relevance. Through this approach, we identified GON4L as a regulator of CD24 from screening a pooled shRNA library of 176 candidate gain-of-function genes. GON4L depletion reduced CD24 expression in human bladder cancer cells and blocked cell proliferation in vitro and tumor xenograft growth in vivo Mechanistically, GON4L interacted with transcription factor YY1, promoting its association with the androgen receptor to drive CD24 expression and cell growth. In clinical bladder cancer specimens, expression of GON4L, YY1, and CD24 was elevated compared with normal bladder urothelium. This pathway is biologically relevant in other cancer types as well, where CD24 and the androgen receptor are clinically prognostic, given that silencing of GON4L and YY1 suppressed CD24 expression and growth of human lung, prostate, and breast cancer cells. Overall, our results define GON4L as a novel driver of cancer growth, offering new biomarker and therapeutic opportunities. Cancer Res; 76(17); 5175-85. ©2016 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Agarwal N,Dancik GM,Goodspeed A,Costello JC,Owens C,Duex JE,Theodorescu Ddoi
10.1158/0008-5472.CAN-16-1099subject
Has Abstractpub_date
2016-09-01 00:00:00pages
5175-85issue
17eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-16-1099journal_volume
76pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::A number of successful systemic therapies are available for treatment of disseminated cancers. However, tumor response is often transient, and therapy frequently fails due to emergence of resistant populations. The latter reflects the temporal and spatial heterogeneity of the tumor microenvironment as well as the evol...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-3658
更新日期:2009-06-01 00:00:00
abstract::Mutations that alter normal splice patterns and genomic rearrangements are common causes of hereditary diseases including hereditary nonpolyposis colorectal cancer. However, abnormal transcripts can be difficult to detect and interpret because splicing patterns are often heterogeneous even in normal cells. Standard te...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-08-15 00:00:00
abstract::The difficulty to dissect a complex phenotype of established malignant cells to several critical transcriptional programs greatly impedes our understanding of the malignant transformation. The genetic elements required to transform some primary human cells to a tumorigenic state were described in several recent studie...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-3880
更新日期:2005-06-01 00:00:00
abstract::The rapidly expanding understanding of the progressive processes of carcinogenesis provides opportunities for the identification of molecular biological markers reflecting events from exposure through clinical disease. These molecular biological markers can be classified into categories of markers of exposure reflecti...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:
更新日期:1994-04-01 00:00:00
abstract::Tbx3 encodes a transcriptional repressor that is important for diverse patterning events during development, and Tbx3 mutation in humans causes the ulnar-mammary syndrome. Here, we describe the identification of Tbx3 in array-based search for genes downstream Wnt/beta-catenin that are implicated in liver tumorigenesis...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-2344
更新日期:2007-02-01 00:00:00
abstract::To identify CpG islands differentially methylated in pancreatic adenocarcinoma, we used methylated CpG island amplification (MCA) coupled with representational difference analysis. Of 42 CpG islands identified by MCA/representational difference analysis, 7 CpG islands [methylated in carcinoma of the pancreas (MICP)] w...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-12-01 00:00:00
abstract::Isozymes of carbamyl phosphate synthetase (CPS), CPS I, a mitochondrial enzyme found exclusively in liver and involved in urea synthesis, and of CPS II, a soluble cytoplasmic enzyme widely distributed in animal tissues, were assayed in rat liver and in a series of rat liver neoplasms ranging widely in growth rate and ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-01-01 00:00:00
abstract::The prostate-specific antigen (PSA) promoter (PSA-P) has been identified, characterized, and determined to be tissue specific. Compared with high expression of the genomic PSA gene in prostate cells, expression of the transgene driven by the putative PSA promoter is low. This suggests that the identified promoter may ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::Astrocytoma, the most common brain tumor in humans, is usually malignant and virtually incurable. Two types of malignant astrocytomas can be distinguished histopathologically: anaplastic astrocytoma and glioblastoma multiforme. Studies using DNA markers that detect restriction fragment length polymorphisms have shown ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-09-15 00:00:00
abstract::C19ORF5 is a sequence homologue of microtubule-associated proteins MAP1A/MAP1B of unknown function, except for its association with mitochondria-associated proteins and the paclitaxel-like microtubule stabilizer and candidate tumor suppressor RASSF1A. Here, we show that when overexpressed in mammalian cells the recomb...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-3865
更新日期:2005-05-15 00:00:00
abstract::We have examined the distribution of radiolabeled liposomes in tumor-bearing mice after i.v. injection. Two mouse tumors (B16 melanoma, J6456 lymphoma) and a human tumor (LS174T colon carcinoma) inoculated i.m., s.c., or in the hind footpad were used in these studies. When various liposome compositions with a mean ves...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
abstract::We evaluated the usefulness of L-dopa decarboxylase (DDC) as a tumor marker of neuroendocrine (NE) cell differentiation by measuring its expression in 432 human tumors of diverse types and origins. A subset of these tumors and cell lines derived from them also were studied for expression of two other general NE cell m...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-07-15 00:00:00
abstract::Over the past 10 years, the Tumor Microenvironment Network (TMEN), supported by the NCI (Bethesda, MD), has promoted collaborative research with the explicit goal of fostering multi-institutional and transdisciplinary groups that are capable of addressing complex issues involving the tumor microenvironment. The main g...
journal_title:Cancer research
pub_type:
doi:10.1158/0008-5472.CAN-16-1336
更新日期:2017-03-01 00:00:00
abstract::Genetic instability, a hallmark feature of human cancers including prostatic adenocarcinomas, is considered a driver of metastasis. Somatic copy number alterations (CNA) are found in most aggressive primary human prostate cancers, and the overall number of such changes is increased in metastases. Chromosome 10q23 dele...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-3280
更新日期:2016-01-15 00:00:00
abstract::Inactivation of the p53 tumor suppressor gene is a common finding in human cancer. In most cases, inactivation is due to a point mutation in the gene, but rearrangement of the p53 gene is sometimes observed. We analyzed the inactivation of p53 in the human pancreas cancer cell line Hs766T, which harbors a structural a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::A synthetic peptide from the inner globule of the B1 chain of laminin, termed peptide F-9 (RYVVLPRPVCFEKGMNYTVR; residues 641-660), has been shown to have heparin-binding and cell adhesion-promoting activities for diverse cell types (Charonis et al., J. Cell. Biol., 107: 1253-1260, 1988). In this study, the metastatic...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-12-01 00:00:00
abstract::Micropthalmia transcription factor (Mitf) is involved in melanocyte development and differentiation. The current study was undertaken to determine whether there is a relationship between Mitf expression and survival in patients with intermediate-thickness (1.0-4.0 mm) melanoma. Original paraffin blocks or slides of th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-09-15 00:00:00
abstract::The effect of the AC33 tumor on protein synthesis in Lewis-Wistar rats was investigated under four different dietary regimens. The four diets used were: (a) 1.25 g amino acids plus 12.5 g glucose per day, (b) 1.25 g amino acids, (c) 1.25 g glucose per day, and (d) 12.5 g glucose per day. The rats were maintained on th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-11-01 00:00:00
abstract::IA-1 is a recently isolated novel complementary DNA which encodes a protein of 510 amino acids that contains both a zinc finger DNA-binding domain and a putative prohormone domain. mRNA expression of IA-1 has been found thus far only in tumors of neuroendocrine origin. In this report we describe the expression of IA-1...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-09-15 00:00:00
abstract::Leukemia following chemotherapy for breast cancer was studied among patients diagnosed during 1973-1985 within the population-based tumor registries in the Surveillance, Epidemiology, and End Results Program. Among 13,734 women given initial chemotherapy, 24 developed acute nonlymphocytic leukemia (ANLL) compared to 2...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract::Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. On the basis of its histopathology and molecular-genomic changes, ovarian cancer has been divided into subtypes, each with distinct biology and outcome. The aim of this study was to develop a panel of patient-derived EOC xenografts that recapit...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-0274
更新日期:2014-12-01 00:00:00
abstract::Prostate tumor cells, which characteristically metastasize to bone, initiate binding interactions with bone marrow endothelium under blood flow conditions through binding interactions with E-selectin. We hypothesized that E-selectin ligands on prostate tumor cells are directly associated with bone-metastatic potential...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-4653
更新日期:2005-07-01 00:00:00
abstract::Early diagnosis of lung cancer based on conventional screening procedures has been unable thus far to decrease lung cancer mortality. We explored the possibility of using microsatellite instability in the detection and screening of early phases of lung carcinogenesis. We studied tumor, histopathologically normal bronc...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-05-15 00:00:00
abstract::A cohort of 17,633 white males age 35 and older responded to a mailed epidemiological questionnaire in 1966 and was followed until 1986 to determine the risk of cancer associated with diet, tobacco use, and other factors. During the 20-year follow-up, 149 fatal prostate cancer cases were identified. Relative risks for...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-11-01 00:00:00
abstract::Several studies have shown that neuroblastoma and retinoblastoma tumor cells often have elevated N-myc mRNA levels compared to normal adult neuronal or retinal tissues, and it has been suggested that increased expression of this protooncogene may play an important role in tumorigenesis or malignant progression in cell...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::Tasidotin (ILX-651), an orally active synthetic microtubule-targeted derivative of the marine depsipeptide dolastatin-15, is currently undergoing clinical evaluation for cancer treatment. Tasidotin inhibited proliferation of MCF7/GFP breast cancer cells with an IC(50) of 63 nmol/L and inhibited mitosis with an IC(50) ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3065
更新日期:2007-04-15 00:00:00
abstract::N'-[2-chloroethyl]-N[2-(methylsulfonyl) ethyl]-N'-nitrosourea (cystemustine),a chloroethylnitrosourea antineoplastic drug, provokes cellular proliferation inhibition and redifferentiation, but there was no cell death in B16 melanoma tumors. Because the phospholipid (Plp) metabolism is tightly involved in tumor growth ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-03-15 00:00:00
abstract::5,6-Dimethylxanthenone-4-acetic acid (DMXAA) and combretastatin A4 phosphate (CA-4-P) markedly inhibit tumor blood flow in mice and are both currently in clinical trial. One of the challenges in clinical evaluation of antivascular agents is the monitoring of tumor blood flow inhibition in individual patients. This stu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-08-15 00:00:00
abstract::It is becoming increasingly clear that tumor growth and progression is not entirely due to genetic aberrations but also reflective of tumor cell plasticity. It follows therefore that proteins contributing to tumor progression oscillate in their expression a contention yet to be shown. Because the urokinase-type plasmi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-3208
更新日期:2006-08-15 00:00:00
abstract::Specific inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) have been developed that efficiently inhibit the oncogenic RAF-MEK-ERK pathway. We used a systems-based approach to identify breast cancer subtypes particularly susceptible to MEK inhibitors and to understa...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-3389
更新日期:2009-01-15 00:00:00