ArticleNature communications2021
Hyperactivation of HER2-SHCBP1-PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Efficacy and safety of antibody-drug conjugates in HER2-positive and HER2-low advanced gastric cancer: a systematic review and update.Journal of the Egyptian National Cancer Institute · 2026Pooled it
- A study on the mechanism of action of B7H4 in HER2-positive gastric cancer and its sensitivity to trastuzumab therapy.Translational cancer research · 2026Article
- A ternary association of KRas, EphA2, and integrins controls PDAC cell behavior.The Journal of biological chemistry · 2026Article
- SHCBP1 Is Upregulated in Colon Adenocarcinoma and Promotes Tumor Cell Proliferation and Growth.Current oncology (Toronto, Ont.) · 2026Article
- Mechanistic study of TIMM44 mediating gastric carcinogenesis via the Gαi1-PI3K-AKT-mTOR signaling pathway.Scientific reports · 2026Article
- Leveraging a chromosomal instability-based signature to predict the prognosis and immune landscape of breast cancer.Genes & diseases · 2026Article
- Advances regarding physiological functions and mechanisms of theaflavin‑3,3'‑digallate (Review).Molecular medicine reports · 2026Review
- Impact of immune microenvironment on immune checkpoint inhibitor response in HER2-overexpressing urothelial carcinoma.Discover oncology · 2026Article
- AXL-SHC1 signaling axis mediates adaptive resistance to HER2-targeted tyrosine kinase inhibitors in HER2-aberrant lung and gastric cancers.NPJ precision oncology · 2026Article
- Targeting PLK1 potentiates the antitumor efficacy of EGFR-TKIs through inhibiting the JAK1/STAT3 pathway.Cell death & disease · 2026Article
- A system-wide investigation into the phosphoregulatory network of TNIK and its cellular implications.Frontiers in bioinformatics · 2026Article
- TRIM47-facilitated PLK1 stabilization promotes the proliferation of liver cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Review
- Discussion on the mechanism of HER2 resistance in esophagogastric junction and gastric cancer in the era of immunotherapy.Human vaccines & immunotherapeutics · 2025Review
- The Roles of SHCBP1 in Cancer Hallmarks: Molecular Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2025Review
- MCM7 promotes liver fibrosis by transcriptionally regulating IL11 via the SHCBP1-RACGAP1-STAT3 axis.Cell death & disease · 2025Article
- Four-gene Prognostic Signature and Risk of Brain Metastasis of Lung Adenocarcinoma.Molecular carcinogenesis · 2025Article
- A risk model based on signature genes predicts prognosis and associates with tumor immunity, drug sensitivity in breast cancer.Cancer biomarkers : section A of Disease markers · 2025Article
- PLK1 Downregulation Attenuates ET-1-Induced Cardiomyocyte Hypertrophy by Suppressing the ERK1/2 Pathway.Journal of cardiovascular translational research · 2025Article
- Hedgehog inhibitors exert anti-proliferation effects and synergistically interact with trastuzumab in HER2-positive gastric cancer models.Acta oncologica (Stockholm, Sweden) · 2025Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trastuzumab is the backbone of HER2-directed gastric cancer therapy, but poor patient response due to insufficient cell sensitivity and drug resistance remains a clinical challenge. Here, we report that HER2 is involved in cell mitotic promotion for tumorigenesis by hyperactivating a crucial HER2-SHCBP1-PLK1 axis that drives trastuzumab sensitivity and is targeted therapeutically. SHCBP1 is an Shc1-binding protein but is detached from scaffold protein Shc1 following HER2 activation. Released SHCBP1 responds to HER2 cascade by translocating into the nucleus following Ser273 phosphorylation, and then contributing to cell mitosis regulation through binding with PLK1 to promote the phosphorylation of the mitotic interactor MISP. Meanwhile, Shc1 is recruited to HER2 for MAPK or PI3K pathways activation. Also, clinical evidence shows that increased SHCBP1 prognosticates a poor response of patients to trastuzumab therapy. Theaflavine-3, 3'-digallate (TFBG) is identified as an inhibitor of the SHCBP1-PLK1 interaction, which is a potential trastuzumab sensitizing agent and, in combination with trastuzumab, is highly efficacious in suppressing HER2-positive gastric cancer growth. These findings suggest an aberrant mitotic HER2-SHCBP1-PLK1 axis underlies trastuzumab sensitivity and offer a new strategy to combat gastric cancer.
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