Abstract:
:Downregulation of the cellular retinol-binding protein-I (CRBP-I) occurs in breast and other human cancers, but its significance is not well understood. Recently, we showed that restoration of CRBP-I expression in transformed MTSV1-7 breast epithelial cells increased retinoic receptor activity, inhibited anoikis, promoted acinar differentiation and inhibited tumorigenicity, suggesting that CRBP-I suppresses tumor progression. However, the mechanism underlying these effects of CRBP-I was not elucidated. Here we demonstrate, using genetic and pharmacological approaches, that CRBP-I inhibits, in a retinoic acid receptor-dependent manner, the PI3K/Akt survival pathway. Inhibition of PI3K/Akt was necessary and sufficient to explain the antitumor effects of CRBP-I and was mediated by decreased p85 regulatory and p110 catalytic subunit heterodimerization. We present evidence consistent with the idea that this effect is due to CRBP-I inhibition of p85 phosphorylation at Y688. To our knowledge, this is the first demonstration of PI3K regulation at the level of p85-p110 heterodimerization. These findings lead us to hypothesize that CRBP-I downregulation in cancer promotes tumor progression through inhibition of retinoic acid receptor activity and derepression of PI3K/Akt signaling via a novel mechanism.
journal_name
Oncogenejournal_title
Oncogeneauthors
Farias EF,Marzan C,Mira-y-Lopez Rdoi
10.1038/sj.onc.1208347subject
Has Abstractpub_date
2005-02-24 00:00:00pages
1598-606issue
9eissn
0950-9232issn
1476-5594pii
1208347journal_volume
24pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in malignant rhabdoid tumors (MRT) and atypical teratoid/rhabdoid tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. SMARCB1 is a core subunit of Swi/Snf chromatin remodeling complexes, and loss ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.261
更新日期:2014-06-05 00:00:00
abstract::Krüppel-like factor 8 (KLF8) is a transcriptional factor critical for metastatic progression of breast cancer. Epithelial stromal interaction 1 (EPSTI1), a recently identified stromal fibroblast-induced gene in non-invasive breast cancer cells is highly overexpressed in invasive breast carcinomas. The function and reg...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.415
更新日期:2014-09-25 00:00:00
abstract::Wnt signaling plays an important role in embryonic development and tumorigenesis. These biological effects are exerted by activation of the beta-catenin/TCF transcription complex and consequent regulation of a set of downstream genes. TCF-binding elements have been found in the promoter regions of many TCF target gene...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207892
更新日期:2004-11-04 00:00:00
abstract::Breast carcinoma invasion is associated with prominent alterations in stromal fibroblasts. Carcinoma-associated fibroblasts (CAF) support and promote tumorigenesis, whereas normal mammary fibroblasts (NF) are thought to suppress tumor progression. Little is known about the difference in gene expression between CAF and...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.463
更新日期:2010-03-25 00:00:00
abstract::It has recently been shown that the high-risk human papillomavirus (HPV) E6 proteins can target the PDZ-domain containing proteins, Dlg, MUPP-1, MAGI-1 and hScrib for proteasome-mediated degradation. However, the E6 proteins from HPV-16 and HPV-18 (the two most common high-risk virus types) differ in their ability to ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204719
更新日期:2001-09-06 00:00:00
abstract::The human MSH2/6 complex is essential for mismatch recognition during the repair of replication errors. Although mismatch repair components have been implicated in DNA homologous recombination repair, the exact function of hMSH2/6 in this pathway is unclear. Here, we show that the recombinant hMSH2/6 protein complex s...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207462
更新日期:2004-05-06 00:00:00
abstract::Smad4 is a critical component in transforming growth factor beta (TGF-beta) signaling and frequently mutated in pancreatic and colorectal cancers. Smad4 has two important functional domains, MH1 and MH2, that are involved in different biological processes. The MH1 domain comprises a DNA binding domain and the MH2 doma...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207219
更新日期:2004-02-05 00:00:00
abstract::Chromosome 1p36.23 is frequently deleted in glioblastoma multiforme (GBM). miR-34a localizes in this region. Our experiments found that miR-34a was often deleted and epidermal growth factor receptor (EGFR) was frequently amplified in genomic DNA of 55 GBMs using single-nucleotide polymorphism DNA microarray. Notably, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.132
更新日期:2013-02-28 00:00:00
abstract::The Abelson (Abl) family of non-receptor tyrosine kinases has an important role in cell morphogenesis, motility, and proliferation. Although the function of Abl has been extensively studied in leukemia, its role in epithelial cell invasion remains obscure. Using the Drosophila wing epithelium as an in vivo model syste...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.155
更新日期:2010-07-15 00:00:00
abstract::In the published version of this paper the author Shu-Pin Huang's surname was incorrectly given as Hwang instead of Huang. This has now been corrected in the HTML and PDF versions of the paper. ...
journal_title:Oncogene
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41388-018-0561-0
更新日期:2019-02-01 00:00:00
abstract::We have previously reported that there is a high incidence of microsatellite instability (MSI) and germline mismatch repair gene mutation in colorectal cancer arising from young Hong Kong Chinese. Most of the germline mutations involve hMSH2, which is different from the mutation spectrum in the Western population. It ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204376
更新日期:2001-05-24 00:00:00
abstract::Matrilysin (MMP-7) is thought to contribute to invasive growth and metastasis of colon carcinoma and many other human cancers. The present study demonstrates that treatment of human colon carcinoma cells with active matrilysin induces cell aggregation in vitro and promotes liver metastasis in nude mice. When two kinds...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207181
更新日期:2003-11-27 00:00:00
abstract::Metabolic acid production challenges cellular pH homeostasis in solid cancer tissue, and mechanisms of net acid extrusion represent promising new targets for breast cancer therapy. Here, we used genetically engineered mice to investigate the contribution of the Na+,HCO3--cotransporter NBCn1 (Slc4a7) to intracellular a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0353-6
更新日期:2018-10-01 00:00:00
abstract::Vascular endothelial (VE)-cadherin is exclusively expressed at interendothelial junctions of normal and tumour vessels. In this report, we characterized the transcriptional activity of the human VE-cadherin promoter. Transient transfection assays revealed that sequences at positions --1135/-744 and -166/-5 base pairs ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208483
更新日期:2005-04-21 00:00:00
abstract::The metastasis-associated protein 1 (MTA1) is overexpressed in various human cancers and is closely connected with aggressive phenotypes; however, little is known about the transcriptional regulation of the MTA1 gene. This study identified the MTA1 gene as a target of p53-mediated transrepression. The MTA1 promoter co...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.2
更新日期:2012-12-06 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::Amplification of the N-myc gene is a significant adverse prognostic factor in neuroblastoma, a common childhood tumor. In non-transformed cells, myc expression is controlled through an autoregulatory circuit, through which elevated Myc protein levels lead to down-regulation of myc transcription. The precise mechanism ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201363
更新日期:1997-10-16 00:00:00
abstract::Pretreatment of cells with 0.5 mM sodium arsenite (but not other activators of stress-activated MAP kinase cascades) prevents the activation of p21Ras and strongly suppresses the activation of c-Raf and the MAP kinase cascade by a variety of growth factors. Arsenite appears to exert its effect by preventing the guanin...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202168
更新日期:1998-07-09 00:00:00
abstract::Oncogenic RAS promotes production of reactive oxygen species (ROS), which mediate pro-malignant signaling but can also trigger DNA damage-induced tumor suppression. Thus RAS-driven tumor cells require redox-protective mechanisms to mitigate the damaging aspects of ROS. Here, we show that MutT Homolog 1 (MTH1), the mam...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.195
更新日期:2015-05-14 00:00:00
abstract::In the course of screening for inhibitors of tumorigenic phenotype of K-ras-transformed NIH3T3 cells (DT cells), we found a novel compound, oxamflatin, an aromatic sulfonamide hydroxamate derivative, which induces flat phenotype in these cells and suppresses their anchorage-independent growth. In contrast to DT cells,...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-07-04 00:00:00
abstract::Procollagen lysyl hydroxylase 1 (PLOD1) is highly expressed in malignant tumors such as esophageal squamous cell carcinoma, gastric cancer, and colorectal cancer. Bioinformatics analysis revealed that PLOD1 is associated with the progression of GBM, particularly the most malignant mesenchymal subtype (MES). Moreover, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-01635-y
更新日期:2021-01-08 00:00:00
abstract::Alpha-fetoprotein (AFP) producing gastric cancer (AFP-GC) is very malignant and highly metastatic compared with common gastric cancer. However, the causal relationship between AFP production and the high malignancy of AFP-GC is unclear. We investigated AFP gene regulation in AFP-GC by an active transcription factor, H...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204160
更新日期:2001-02-15 00:00:00
abstract::Forkhead box O class transcription factors are homeostasis regulators that control cell death, longevity and therapy-resistance. In neuroblastoma (NB), nuclear FOXO3 correlates with stage M disease and poor prognosis. To analyze whether FOXO3 contributes to drug-resistance in this childhood cancer, we investigated how...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.288
更新日期:2017-11-02 00:00:00
abstract::GATA3 is an essential transcription factor that was first identified as a regulator of immune cell function. In recent microarray analyses of human breast tumors, both normal breast luminal epithelium and estrogen receptor (ESR1)-positive tumors showed high expression of GATA3. We sequenced genomic DNA from 111 breast...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207966
更新日期:2004-10-07 00:00:00
abstract::Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapy because of its relative tumor selectivity. However, many cancers including pancreatic cancer remain resistant towards TRAIL. To develop TRAIL for cancer therapy of pancreatic carcinoma, it will therefore b...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209776
更新日期:2007-01-11 00:00:00
abstract::Making decisions between self-renewal and differentiation is a central ability of stem cells. Elucidation of molecular networks governing this decision is therefore of prime importance. A model of choice to explore this question is represented by chicken erythroid progenitors, in which self-renewal versus differentiat...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207049
更新日期:2003-12-18 00:00:00
abstract::Despite the progress made in targeted anticancer therapies in recent years, challenges remain. The identification of new potential targets will ensure that the arsenal of cancer therapies continues to expand. FAM83B was recently discovered in a forward genetic screen for novel oncogenes that drive human mammary epithe...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.293
更新日期:2014-06-19 00:00:00
abstract::The RASSF8 gene, which maps close to the KRAS2 gene, contains a RAS-associated domain and encodes a protein that is evolutionarily conserved from fish to humans. Analysis of the RASSF8 transcript revealed a complex expression pattern of 5'-UTR mRNA isoforms in normal lung and in lung adenocarcinomas (ADCAs), with no a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209422
更新日期:2006-06-29 00:00:00
abstract::The epithelium-specific transcription factor, ERT/ESX/ESE-1/ELF3, binds to the TGF-beta RII promoter in a sequence specific manner and regulates its expression. In this study, we investigated whether ERT could regulate endogenous TGF-beta RII expression in Hs578t breast cancer cells. Analyses of the Hs578t parental ce...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203252
更新日期:2000-01-06 00:00:00
abstract::Emerging evidence has shown that cancer stem cells (CSCs) are the cellular determinants to promote cancer invasion and metastasis. However, the mechanism underlying CSC invasion remains unknown. MicroRNAs are evolutionally conserved small noncoding RNAs that are critical for the regulation of gene expression, and thei...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.75
更新日期:2015-03-12 00:00:00