ArticlePloS one2014
Modulation of ErbB2 blockade in ErbB2-positive cancers: the role of ErbB2 Mutations and PHLDA1.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Meta-analysis of gene expression profiles in long-term non-progressors infected with HIV-1.BMC medical genomics · 2019Pooled it
- Spatiotemporal multi-omics analysis uncovers NAD-dependent immunosuppressive niche triggering early gastric cancer.Signal transduction and targeted therapy · 2025Article
- TDAG51 Mediates Negative Signaling Crosstalk Between NGF/p75Neurochemical research · 2025Article
- Expanding on roles of pleckstrin homology-like domain family A member 1 protein.Cell and tissue research · 2025Review
- Multiomics Analysis of the PHLDA Gene Family in Different Cancers and Their Clinical Prognostic Value.Current issues in molecular biology · 2024Article
- PHLDA1 is a P53 target gene involved in P53-mediated cell apoptosis.Molecular and cellular biochemistry · 2024Article
- Silencing of theFrontiers in pharmacology · 2024Article
- FGF10 mitigates doxorubicin-induced myocardial toxicity in mice via activation of FGFR2b/PHLDA1/AKT axis.Acta pharmacologica Sinica · 2023Article
- PHLDA1 promotes glioblastoma cell growth via sustaining the activation state of Ras.Cellular and molecular life sciences : CMLS · 2022Article
- AnEuropean journal of breast health · 2022Article
- The expression patterns and prognostic significance of pleckstrin homology-like domain family A (PHLDA) in lung cancer and malignant mesothelioma.Journal of thoracic disease · 2021Article
- T-Cell Death Associated Gene 51 Is a Novel Negative Regulator of PPARγ That Inhibits PPARγ-RXRα Heterodimer Formation in AdipogenesisMolecules and cells · 2021Article
- PHLD Class Proteins: A Family of New Players in the p53 Network.International journal of molecular sciences · 2020Review
- Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity.International journal of molecular sciences · 2020Review
- High Frequency ofCancers · 2019Article
- PHLDA1, another PHLDA family protein that inhibits Akt.Cancer science · 2018Article
- Transcriptome Profiling Reveals PHLDA1 as a Novel Molecular Marker for Ischemic Cardiomyopathy.Journal of molecular neuroscience : MN · 2018Article
- PHLDA1 Mediates Drug Resistance in Receptor Tyrosine Kinase-Driven Cancer.Cell reports · 2018Article
- Transcriptionally inducible Pleckstrin homology-like domain, family A, member 1, attenuates ErbB receptor activity by inhibiting receptor oligomerization.The Journal of biological chemistry · 2018Article
- PHLDA1 (pleckstrin homology-like domain, family A, member 1) knockdown promotes migration and invasion of MCF10A breast epithelial cells.Cell adhesion & migration · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We set out to study the key effectors of resistance and sensitivity to ErbB2 tyrosine kinase inhibitors, such as lapatinib in ErbB2-positive breast and lung cancers. A cell-based in vitro site-directed mutagenesis lapatinib resistance model identified several mutations, including the gatekeeper ErbB2 mutation ErbB2-T798I, as mediating resistance. ErbB2-T798I engineered cell models indeed show resistance to lapatinib but remain sensitive to the irreversible EGFR/ErbB2 inhibitor, PD168393, suggestive of potential alternative treatment strategies to overcome resistance. Gene expression profiling studies identified a select group of downstream targets regulated by ErbB2 signaling and define PHLDA1 as an immediately downregulated gene upon oncogenic ErbB2 signaling inhibition. We find significant down-regulation of PHLDA1 in primary breast cancer and PHLDA1 is statistically significantly less expressed in ErbB2 negative compared with ErbB2 positive tumors consistent with its regulation by ErbB2. Lastly, PHLDA1 overexpression blocks AKT signaling, inhibits cell growth and enhances lapatinib sensitivity further supporting an important negative growth regulator function. Our findings suggest that PHLDA1 might have key inhibitory functions in ErbB2 driven lung and breast cancer cells and a better understanding of its functions might point at novel therapeutic options. In summary, our studies define novel ways of modulating sensitivity and resistance to ErbB2 inhibition in ErbB2-dependent cancers.
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.