ArticleCancer research2018
HER2 Amplification in Tumors Activates PI3K/Akt Signaling Independent of HER3.
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
What it found
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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.
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Who cites it
93 citing papers in PubMed, 139 citations in OpenAlex.
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Article
- HER2-driven mammary tumorigenesis enhances bioenergetics despite reductions in mitochondrial content.eLife · 2026Article
- CancerOmicsStudio (CoS): a web server for integrative and interpretable analysis of multi-omics cancer data.Bioinformatics (Oxford, England) · 2026Article
- IRS4 is a PI3K-activating cancer dependency up-regulated through DNA rearrangements or epigenetic mechanisms in multiple solid tumors.Science advances · 2026Article
- EpCAM-PSMA: Potential predictors of treatment outcomes for PSMA-targeted alpha therapies in metastatic castration-resistant prostate cancer.Molecular therapy. Oncology · 2026Article
- Targeting HSP90 in cancer: advances in the development of inhibitors, mechanisms of action, and therapeutic applications.Molecular cancer · 2026Review
- Oncogenic Alterations in PI3K Signaling Emulated Optogenetically Recapitulate Some Phenotypic Changes in Mammary Epithelia.ACS synthetic biology · 2026Article
- CAR-T cell immunotherapy in rhabdomyosarcoma.Journal of translational medicine · 2026Review
- Neuregulin induces prostate cancer cell migration via HER3/HER2-FAK/Src signaling axis.Cancer cell international · 2026Article
- Promising Targets and Drugs for Improving Head and Neck Cancer Response to Radiotherapy.Current pharmaceutical design · 2026Review
- Correlation analysis of serum amyloid A, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammation index with neoadjuvant therapy efficacy and prognosis in breast cancer.Frontiers in oncology · 2026Article
- Evolving treatment strategies for HER2-altered non-small-cell lung cancer: the rise of TKIs and ADCs.Frontiers in oncology · 2026Review
- Semiquantitative immunohistochemical (IHC) pixelwise H-score of mitochondrial transcription factor A (TFAM) in gastric adenocarcinoma (GAC): clinicopathological significance and association with p53 and HER2.World journal of surgical oncology · 2025Article
- Dual Role of Diallyl Disulfide (DADS) on Invasive Potential and β-Catenin Dynamics in HER2-Positive Breast Cancer Cells.Cancers · 2025Article
- HER2 as a molecular trojan horse in prostate cancer: mechanistic insights and therapeutic unlocks.Molecular biology reports · 2025Review
- Advancements in Targeted Therapies for Colorectal Cancer: Overcoming Challenges and Exploring Future Directions.Cancers · 2025Review
- Discovery of natural scaffolds as HER2 inhibitors for breast cancer: virtual screening, molecular dynamics, and biological characterization with selectivity profiling.Scientific reports · 2025Article
- HER3: Unmasking a twist in the tale of a previously unsuccessful therapeutic pursuit targeting a key cancer survival pathway.Genes & diseases · 2025Review
- Factors Associated With Short- and Long-Term Survival in Metastatic HER2-Positive Breast Cancer.Clinical breast cancer · 2025Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Current evidence suggests that HER2-driven tumorigenesis requires HER3. This is likely due to the unique ability of HER3 to activate PI3K/Akt pathway signaling, which is not directly accessible to HER2. By genetic elimination of HER3 or shRNA knockdown of HER3 in HER2-amplified cancer cells, we find residual HER2-driven activation of PI3K/Akt pathway signaling that is driven by HER2 through direct and indirect mechanisms. Indirect mechanisms involved second messenger pathways, including Ras or Grb2. Direct binding of HER2 to PI3K occurred through p-Tyr1139, which has a weak affinity for PI3K but becomes significant at very high expression and phosphorylation. Mutation of Y1139 impaired the tumorigenic competency of HER2. Total elimination of HER3 expression in HCC1569 HER2-amplified cancer cells significantly impaired tumorigenicity only transiently, overcome by subsequent increases in HER2 expression and phosphorylation with binding and activation of PI3K. In contrast to activation of oncogenes by mutation, activation by overexpression was quantitative in nature: weak intrinsic activities were strengthened by overexpression, with additional gains observed through further increases in expression. Collectively, these data show that progressive functional gains by HER2 can increase its repertoire of activities such as the activation of PI3K and overcome its dependency on HER3.
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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.