Abstract:
:Tumor suppressor genes and the immune system are critical players in inhibiting cancer initiation and/or progression. However, little is known about whether a tumor suppressor gene can function through both immune-dependent and -independent mechanisms. Retinoic acid receptor responder 2 (RARRES2) is transcriptionally downregulated in multiple cancer types. Previous studies suggested that it can serve as an immune-dependent tumor suppressor by acting as a chemoattractant to recruit anticancer immune cells expressing its receptor, the chemerin chemokine receptor 1 (CMKLR1), to sites of tumor. In this study, we investigated the role of RARRES2 in adrenocortical carcinoma (ACC), a rare lethal malignancy in which aberrant Wnt/β-catenin signaling is frequently detected. We show that RARRES2 expression is downregulated in ACC as compared with normal and benign adrenocortical tissues, which is a result of CpG hypermethylation. Despite minimal CMKLR1 expression and lack of phenotypic tumor-suppressive effect with exogenous RARRES2 treatment, RARRES2 overexpression in ACC cell lines not only reduced cell proliferation, cell invasion and tumorigenicity in vitro, but also inhibited tumor growth in vivo in two immunodeficient mouse xenograft models. Mechanistically, RARRES2 overexpression in ACC cells inhibited Wnt/β-catenin pathway activity by promoting β-catenin phosphorylation and degradation, it also inhibited the phosphorylation of p38 mitogen-activated protein kinase. Thus our study identifies RARRES2 as a novel tumor suppressor for ACC, which can function through an immune-independent mechanism.
journal_name
Oncogenejournal_title
Oncogeneauthors
Liu-Chittenden Y,Jain M,Gaskins K,Wang S,Merino MJ,Kotian S,Kumar Gara S,Davis S,Zhang L,Kebebew Edoi
10.1038/onc.2016.497subject
Has Abstractpub_date
2017-06-22 00:00:00pages
3541-3552issue
25eissn
0950-9232issn
1476-5594pii
onc2016497journal_volume
36pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Proteolytic cleavage of the extracellular domain of CD44 from the surface of cells has been observed recently in different cell types. In cell culture supernatants of human melanoma cell lines a 70 kDa soluble CD44 protein (solCD44) was detected at concentrations of 250-300 ng/ml. Protease inhibitor studies revealed t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204435
更新日期:2001-06-07 00:00:00
abstract::The p53 tumor suppressor protein activates transcription and induces cell death. A close homologue of p53, termed p73, is expressed in transactivating (TA) forms that induce growth arrest and apoptosis much like p53. However, the p73 gene contains a second promoter, giving rise to the expression of p73 Delta N, a spec...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205584
更新日期:2002-07-18 00:00:00
abstract::Lung cancer is one of the major causes of cancer death and clarification of its molecular pathology is highly prioritized. The physiological importance of mRNA degradation through the CCR4-NOT deadenylase has recently been highlighted. For example, mutation in CNOT3, a gene coding for CNOT3 subunit of the CCR4-NOT com...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0603-7
更新日期:2019-04-01 00:00:00
abstract::The retinoblastoma gene product (pRb) controls proliferation and differentiation processes in stratified epithelia. Importantly, and in contrast to other tissues, Rb deficiency does not lead to spontaneous skin tumor formation. As the cyclin-dependent kinase inhibitor p21 regulates proliferation and differentiation in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.417
更新日期:2014-09-11 00:00:00
abstract::Activating mutations of the N-ras gene occur at relatively high frequency in acute myeloid leukemia and myelodysplastic syndrome. Somewhat paradoxically, ectopic expression of activated N-ras in primary hematopoietic cells and myeloid cell lines (in some cases) can lead to inhibition of proliferation. Expression of mu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208877
更新日期:2005-11-10 00:00:00
abstract::Since defects in molecular mechanisms controlling DNA repair, cell cycle checkpoint and apoptosis could modify cellular sensitivity to DNA damaging agents, we have conducted a multiparametric molecular analysis for better understanding the regulation pathways leading to cell survival or cell death after irradiation. U...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203405
更新日期:2000-02-17 00:00:00
abstract::Epstein-Barr virus (EBV) transforms resting primary human B lymphocytes into indefinitely proliferating lymphoblastoid cell lines in vitro and is associated with several human malignancies in vivo. Recombinant EBV genetic analyses combined with in vitro B lymphocyte transformation assays demonstrate that latent infect...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1203217
更新日期:1999-11-22 00:00:00
abstract::In this study we have surveyed by immunoblotting the protein levels of Cyclin D1, D2, D3 and their catalytic partners, Cdk4 and Cdk6 in normal and transformed human cells. We found that all these proteins were differentially expressed in diploid cells derived from different tissues, in contrast to Cyclin E, Cyclin A a...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::Small cell lung cancer (SCLC) is an aggressive cancer characterized by several autocrine growth mechanisms including stem cell factor and its receptor c-Kit. In order to arrive at potentially new and novel therapy for SCLC, we have investigated the effects of the tyrosine kinase inhibitor, STI 571, on SCLC cell lines....
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203698
更新日期:2000-07-20 00:00:00
abstract::The HER-2/neu proto-oncogene is homologous with, but distinct from, the epidermal growth factor receptor. Current evidence indicates that this gene is frequently amplified and/or overexpressed in some human breast and ovarian cancers and that these alterations may be clinically important; however, little is known abou...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-07-01 00:00:00
abstract::Treating lung cancer cell lines using low-dose 5-aza-2'-deoxycytidine (DAC) caused an accumulation of procaspase-9 through mRNA upregulation, but the cells did not undergo apoptosis. However, when cells were treated with DAC and infected with a low dose of a recombinant wild-type p53 adenovirus vector (Ad-p53), a syne...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207381
更新日期:2004-09-02 00:00:00
abstract::Glioma stem cells (GSCs) decrease T cells cognition and evade systemic immunosurveillance via downregulations or defects of major histocompatibility complex class I (MHC-I) molecule and antigen-processing machinery (APM) components. Improvement of tumor surface antigens of GSCs may be effective strategy to trigger an ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-1045-6
更新日期:2020-01-01 00:00:00
abstract::The efficacy of anticancer therapy is limited by the development of drug resistance. While the role of p53 in the intrinsic sensitivity of human cancer cells to paclitaxel (PTX) remains controversial, its role in acquired paclitaxel resistance has never been addressed. In this study we examined the p53 status of three...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203642
更新日期:2000-06-22 00:00:00
abstract::By direct sequencing of cosmids using primers designed from the known cDNA sequence, we identified 19 exons in the human MET proto-oncogene, and sequenced the corresponding 5' and 3' exon-intron junctions. By homology search in the database of the Washington University Genome Sequence Center (GSC), we identified one a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201338
更新日期:1997-09-25 00:00:00
abstract::YAP (Yes-associated protein) oncogene has been found to form a stable complex with members of the Angiomotin (Amot) family of proteins, which bind WW domains of YAP and sequester the protein in the cytoplasm and junctional complexes. The Amot-mediated retention of YAP in the cytoplasm results in the inhibition of its ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.216
更新日期:2012-01-05 00:00:00
abstract::Several cytokines, growth factors and the HIV transactivator Tat were shown to be involved in the pathogenesis of Kaposi's sarcoma. BKV/tat transgenic mice develop Kaposi's sarcoma-like lesions, and spindle-shaped cells (TTB) have been derived from these lesions. Here we show that TTB cells co-express hepatocyte growt...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-09-05 00:00:00
abstract::Using test plasmids containing the SV40 origin, we found a wide spectrum of permissiveness to their replication in different human cell lines. N-myc overexpressing neuroblastoma cells were highly permissive. LA-N-1 neuroblastoma cells were the most permissive of all the cell lines that we tested including the homologo...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1991-07-01 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::Cyclooxygenase (COX)-2 is upregulated in hepatocellular carcinoma (HCC). However, the direct causative effect of COX-2 in spontaneous HCC formation remains unknown. We thus investigate the role and molecular pathogenesis of COX-2 in HCC by using liver-specific COX-2 transgenic (TG) mice. We found spontaneous HCC forma...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.73
更新日期:2017-08-01 00:00:00
abstract::Recent studies have revealed that Ras can associate physically with Raf. In the present study, we tested 34 mutants of Ha-Ras carrying substitution(s) in the region of residues 23-71 for their ability to associate with Raf-1. Mouse Ba/F3 cell lysates were incubated with each mutant Ras protein, in either the guanosine...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::The steady-state levels of p53 mRNA were dramatically lower in immortal chicken embryo fibroblast (CEF) cell lines compared to primary CEF cells. In the presence of cycloheximide (CHX), the steady-state levels of p53 mRNA markedly increased in immortal CEF cell lines, similar to levels found in primary cells. The de n...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204664
更新日期:2001-08-23 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::Mcl-1 is an antiapoptotic member of the Bcl-2 family that can promote cell viability. We report here that Mcl-1 is a new substrate for caspases during induction of apoptosis. Mcl-1 cleavage occurs after Asp127 and Asp157 and generates four fragments of 24, 19, 17 and 12 kDa in both intact cells and in vitro, an effect...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208069
更新日期:2004-10-14 00:00:00
abstract::N-cadherin is a cell-cell adhesion molecule that plays a role in breast cancer metastasis. Here, we show that in vivo expression of N-cadherin in the PyMT mouse model, which enhances mammary tumor metastasis, results in selective inhibition of Akt3 expression and phosphorylation. Similarly, exogenous expression of N-c...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.65
更新日期:2013-01-24 00:00:00
abstract::Uterine leiomyomas or fibroids (UFs) are benign tumors characterized by hyperplastic smooth muscle cells and excessive deposition of extracellular matrix (ECM). Afflicting ~80% of women, and symptomatic in 25%, UFs bring tremendous suffering and are an economic burden worldwide; they cause severe pain and bleeding, an...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0808-4
更新日期:2019-07-01 00:00:00
abstract::Small-molecule agonists at Toll-like receptor 7 (TLR7) and TLR8 have sparked a vivid interest in cancer research owing to their profound antitumoral activity. The lead compound of the imidazoquinoline family, imiquimod, is marketed as a topical formulation. It is efficacious against many primary skin tumors and cutane...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1210913
更新日期:2008-01-07 00:00:00
abstract::Oligonucleotide microarray analysis was applied to assess the expression profile of 332 probe sets representing 308 genes or expressed sequence tags (ESTs) that map to chromosome 17 in order to address epigenetic events that result in alterations in gene expression in epithelial ovarian cancer (EOC). Expression profil...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206219
更新日期:2003-03-13 00:00:00
abstract::Epigenetic regulations play crucial roles in leukemogenesis and leukemia progression. SUV39H1 is the dominant H3K9 methyltransferase in the hematopoietic system, and its expression declines with aging. However, the role of SUV39H1 via its-mediated repressive modification H3K9me3 in leukemogenesis/leukemia progression ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-01495-6
更新日期:2020-12-01 00:00:00
abstract::Rel/NF-kappaB transcription factors are involved in several physiological processes, including the regulation of apoptosis. These factors were shown to exhibit pro- or anti-apoptotic activities in different cellular models, but at present, the mechanisms underlying these opposite effects are poorly understood. In this...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205536
更新日期:2002-06-27 00:00:00
abstract::A dominant negative mutant of Ras, M17 Ras, was used to study the role of Ras in receptor coupling of Raf-1 and B-Raf protein serine/threonine kinases (PSKs). We found that mutant Ras blocks serum- and 12-O-tetradecanoyl phorbol 13-acetate-induced activation of Raf-1 kinase in NIH3T3 cells and Raf-1 as well as B-Raf P...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00