ArticleJCI insight2021
Targeting Gi/o protein-coupled receptor signaling blocks HER2-induced breast cancer development and enhances HER2-targeted therapy.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 18 citations in OpenAlex.
- Cancer Neuroscience: From Local Neuro-Immune Microenvironments to Systemic Brain-Body Circuitry.MedComm · 2026Review
- In vivo CRISPR screening links NFKB1 to endocrine resistance in ER+ breast cancer.Endocrine-related cancer · 2026Article
- Pertussis toxin-induced lymphocytosis shifts the tumor microenvironment toward immune activation via CXCL9 signaling.Cancer immunology, immunotherapy : CII · 2026Article
- Targeting tumor-associated G-protein coupled receptors: beyond single-axis inhibition toward multidimensional regulation.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Bombesin Receptor Subtype-3 Regulates Tumor Growth by HER2 Tyrosine Phosphorylation in a Reactive Oxygen Species-Dependent Manner in Lung Cancer Cells.Targets (Basel) · 2025Article
- Unveiling RACK1: a key regulator of the PI3K/AKT pathway in prostate cancer development.Oncogene · 2025Article
- Preclinical and Basic Research Strategies for Overcoming Resistance to Targeted Therapies in HER2-Positive Breast Cancer.Cancers · 2023Review
- Active GαMolecular and cellular biology · 2023Article
- Progesterone activates GPR126 to promote breast cancer development via the Gi pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Molecular Effects of Auto-Antibodies on Angiotensin II Type 1 Receptor Signaling and Cell Proliferation.International journal of molecular sciences · 2022Article
- Article
- Endothelial Cells Promote Migration of Mesenchymal Stem Cells via PDGF-BB/PDGFRStem cells international · 2022Article
- Therapeutic and prognostic potential of GPCRs in prostate cancer from multi-omics landscape.Frontiers in pharmacology · 2022Article
- The History of Pertussis Toxin.Toxins · 2021Review
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
GPCRs are highly desirable drug targets for human disease. Although GPCR dysfunction drives development and progression of many tumors, including breast cancer (BC), targeting individual GPCRs has limited efficacy as a cancer therapy because numerous GPCRs are activated. Here, we sought a new way of blocking GPCR activation in HER2+ BC by targeting a subgroup of GPCRs that couple to Gi/o proteins (Gi/o-GPCRs). In mammary epithelial cells of transgenic mouse models, and BC cell lines, HER2 hyperactivation altered GPCR expression, particularly, Gi/o-GPCR expression. Gi/o-GPCR stimulation transactivated EGFR and HER2 and activated the PI3K/AKT and Src pathways. If we uncoupled Gi/o-GPCRs from their cognate Gi/o proteins by pertussis toxin (PTx), then BC cell proliferation and migration was inhibited in vitro and HER2-driven tumor formation and metastasis were suppressed in vivo. Moreover, targeting Gi/o-GPCR signaling via PTx, PI3K, or Src inhibitors enhanced HER2-targeted therapy. These results indicate that, in BC cells, HER2 hyperactivation drives aberrant Gi/o-GPCR signaling and Gi/o-GPCR signals converge on the PI3K/AKT and Src signaling pathways to promote cancer progression and resistance to HER2-targeted therapy. Our findings point to a way to pharmacologically deactivate GPCR signaling to block tumor growth and enhance therapeutic efficacy.
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.