ArticleCancer prevention research (Philadelphia, Pa.)2011
Targeting p53-null neuroblastomas through RLIP76.
Article in Cancer prevention research (Philadelphia, Pa.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Neuroblastoma response to RAS-MAPK inhibitors and APR-246 (eprenetapopt) co-treatment is dependent on SLC7A11.Frontiers in oncology · 2024Article
- Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer's Disease?International journal of molecular sciences · 2022Review
- Article
- Haploinsufficiency Interactions between RALBP1 and p53 in ERBB2 and PyVT Models of Mouse Mammary Carcinogenesis.Cancers · 2021Article
- RLIP depletion induces apoptosis associated with inhibition of JAK2/STAT3 signaling in melanoma cells.Carcinogenesis · 2021Article
- Activating p53 function by targeting RLIP.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Rlip Depletion Suppresses Growth of Breast Cancer.Cancers · 2020Article
- Inhibitors of ribosome biogenesis repress the growth of MYCN-amplified neuroblastoma.Oncogene · 2019Article
- 2'-Hydroxyflavanone: A novel strategy for targeting breast cancer.Oncotarget · 2017Article
- RLIP76 Inhibition: A Promising Developmental Therapy for Neuroblastoma.Pharmaceutical research · 2017Review
- Review
- RLIP76 Targeted Therapy for Kidney Cancer.Pharmaceutical research · 2015Review
- Oncolytic adenovirus-mediated short hairpin RNA targeting MYCN gene induces apoptosis by upregulating RKIP in neuroblastoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Overexpression of RLIP76 Required for Proliferation in Meningioma Is Associated with Recurrence.PloS one · 2015Article
- P300 regulates the human RLIP76 promoter activity and gene expression.Biochemical pharmacology · 2013Article
- Knockdown of RLIP76 expression by RNA interference inhibits invasion, induces cell cycle arrest, and increases chemosensitivity to the anticancer drug temozolomide in glioma cells.Journal of neuro-oncology · 2013Article
- Didymin induces apoptosis by inhibiting N-Myc and upregulating RKIP in neuroblastoma.Cancer prevention research (Philadelphia, Pa.) · 2012Article
- RLIP76 regulates PI3K/Akt signaling and chemo-radiotherapy resistance in pancreatic cancer.PloS one · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The search for p53-independent mechanism of cancer cell killing is highly relevant to pediatric neuroblastomas, where successful therapy is limited by its transformation into p53-mutant and a highly drug-resistant neoplasm. Our studies on the drug-resistant p53-mutant as compared with drug-resistant p53 wild-type neuroblastoma revealed a novel mechanism for resistance to apoptosis: a direct role of p53 in regulating the cellular concentration of proapoptotic alkenals by functioning as a specific and saturable allosteric inhibitor of the alkenal-glutathione conjugate transporter, RLIP76. The RLIP76-p53 complex was showed by both immunoprecipitation analyses of purified proteins and immunofluorescence analysis. Drug transport studies revealed that p53 inhibited both basal and PKCα-stimulated transport of glutathione conjugates of 4HNE (GSHNE) and doxorubicin. Drug resistance was significantly greater for p53-mutant as compared with p53 wild-type neuroblastoma cell lines, but both were susceptible to depletion of RLIP76 by antisense alone. In addition, inhibition of RLIP76 significantly enhanced the cytotoxicity of cisplatin. Taken together, these studies provide powerful evidence for a novel mechanism for drug and apoptosis resistance in p53-mutant neuroblastoma, based on a model of regulation of p53-induced apoptosis by RLIP76, where p53 is a saturable and specific allosteric inhibitor of RLIP76, and p53 loss results in overexpression of RLIP76; thus, in the absence of p53, the drug and glutathione-conjugate transport activities of RLIP76 are enhanced. Most importantly, our findings strongly indicate RLIP76 as a novel target for therapy of drug-resistant and p53-mutant neuroblastoma.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.