ArticleThe Journal of biological chemistry2011
IQGAP1 protein binds human epidermal growth factor receptor 2 (HER2) and modulates trastuzumab resistance.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The trial behind it
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer.Molecular & cellular proteomics : MCP · 2015Trial
- Queue Gaps Among the IQGAPs inInternational journal of molecular sciences · 2026Review
- Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- The IQGAP scaffolds: Critical nodes bridging receptor activation to cellular signaling.The Journal of cell biology · 2023Review
- Article
- N-Linked Glycosylation in Chinese Hamster Ovary Cells Is Critical for Insulin-like Growth Factor 1 Signaling.International journal of molecular sciences · 2022Article
- CDC42-IQGAP Interactions Scrutinized: New Insights into the Binding Properties of the GAP-Related Domain.International journal of molecular sciences · 2022Article
- Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma.Frontiers in oncology · 2022Review
- Role of IQGAP1 in Carcinogenesis.Cancers · 2021Review
- Proteomic Characterization of Cytoplasmic Lipid Droplets in Human Metastatic Breast Cancer Cells.Frontiers in oncology · 2021Article
- New model for the interaction of IQGAP1 with CDC42 and RAC1.Small GTPases · 2020Review
- The Specificity of EGF-Stimulated IQGAP1 Scaffold Towards the PI3K-Akt Pathway is Defined by the IQ3 motif.Scientific reports · 2019Article
- Acquired Resistance to Drugs Targeting Tyrosine Kinases.Advances in cancer research · 2018Review
- Molecular classifications of gastric cancers: Novel insights and possible future applications.World journal of gastrointestinal oncology · 2017Review
- Absence of IQGAP1 Protein Leads to Insulin Resistance.The Journal of biological chemistry · 2017Article
- Asparaginyl endopeptidase improves the resistance of microtubule-targeting drugs in gastric cancer through IQGAP1 modulating the EGFR/JNK/ERK signaling pathway.OncoTargets and therapy · 2017Article
- IQGAP1 Binds to Yes-associated Protein (YAP) and Modulates Its Transcriptional Activity.The Journal of biological chemistry · 2016Article
- Preclinical evidence of multiple mechanisms underlying trastuzumab resistance in gastric cancer.Oncotarget · 2016Article
- Different Facets of Copy Number Changes: Permanent, Transient, and Adaptive.Molecular and cellular biology · 2016Review
- IQGAP1 promotes CXCR4 chemokine receptor function and trafficking via EEA-1+ endosomes.The Journal of cell biology · 2015Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-25% of breast cancers. Increased HER2 expression is an adverse prognostic factor and correlates with decreased patient survival. HER2-positive (HER2(+)) breast cancer is treated with trastuzumab. Unfortunately, some patients are intrinsically refractory to therapy, and many who do respond initially become resistant within 1 year. Understanding the molecular mechanisms underlying HER2 signaling and trastuzumab resistance is essential to reduce breast cancer mortality. IQGAP1 is a ubiquitously expressed scaffold protein that contains multiple protein interaction domains. By regulating its binding partners IQGAP1 integrates signaling pathways, several of which contribute to breast tumorigenesis. We show here that IQGAP1 is overexpressed in HER2(+) breast cancer tissue and binds directly to HER2. Knockdown of IQGAP1 decreases HER2 expression, phosphorylation, signaling, and HER2-stimulated cell proliferation, effects that are all reversed by reconstituting cells with IQGAP1. Reducing IQGAP1 up-regulates p27, and blocking this increase attenuates the growth inhibitory effects of IQGAP1 knockdown. Importantly, IQGAP1 is overexpressed in trastuzumab-resistant breast epithelial cells, and reducing IQGAP1 both augments the inhibitory effects of trastuzumab and restores trastuzumab sensitivity to trastuzumab-resistant SkBR3 cells. These data suggest that inhibiting IQGAP1 function may represent a rational strategy for treating HER2(+) breast carcinoma.
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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.