ArticleGastroenterology2011
DARPP-32 increases interactions between epidermal growth factor receptor and ERBB3 to promote tumor resistance to gefitinib.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Advances in protein microarray-based proteomics for gastric cancer applications in biomarker discovery, molecular subtyping, and precision oncology.Frontiers in oncology · 2026Review
- CircZFAND6 suppresses gastric cancer metastasis and reduces resistance to TKI therapy.Molecular cancer · 2025Article
- Immunohistochemical characterization and potential prognostic relevance of dopamine signaling in canine pulmonary adenocarcinoma.Frontiers in veterinary science · 2025Article
- Review
- Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer.Cell reports. Medicine · 2024Article
- Smoking induces WEE1 expression to promote docetaxel resistance in esophageal adenocarcinoma.Molecular therapy oncolytics · 2023Article
- IKKα promotes lung adenocarcinoma growth through ERK signaling activation via DARPP-32-mediated inhibition of PP1 activity.NPJ precision oncology · 2023Article
- HER3-targeted therapeutic antibodies and antibody-drug conjugates in non-small cell lung cancer refractory to EGFR-tyrosine kinase inhibitors.Chinese medical journal pulmonary and critical care medicine · 2023Review
- Establishment of head and neck squamous cell carcinoma mouse models for cetuximab resistance and sensitivity.Cancer drug resistance (Alhambra, Calif.) · 2023Article
- Unfolded Protein Response Is Activated by Aurora Kinase A in Esophageal Adenocarcinoma.Cancers · 2022Article
- DARPP-32 promotes ERBB3-mediated resistance to molecular targeted therapy in EGFR-mutated lung adenocarcinoma.Oncogene · 2022Article
- Silencing of miR490-3p by H. pylori activates DARPP-32 and induces resistance to gefitinib.Cancer letters · 2020Article
- ASCL1-regulated DARPP-32 and t-DARPP stimulate small cell lung cancer growth and neuroendocrine tumour cell proliferation.British journal of cancer · 2020Article
- Aberrant expression and regulatory network of splicing factor-SRSF3 in tumors.Journal of Cancer · 2020Review
- Integrated Analysis of Mouse and Human Gastric Neoplasms Identifies Conserved microRNA Networks in Gastric Carcinogenesis.Gastroenterology · 2019Article
- Darpp-32 and t-Darpp protein products of PPP1R1B: Old dogs with new tricks.Biochemical pharmacology · 2019Review
- DARPP-32 and t-DARPP isoform in non-small cell lung cancer (NSCLC): could they drive patients' clinical management and be a therapeutic target?Translational lung cancer research · 2018Article
- DARPP-32 and t-DARPP promote non-small cell lung cancer growth through regulation of IKKα-dependent cell migration.Communications biology · 2018Article
- Evaluation of Protein Levels of the Receptor Tyrosine Kinase ErbB3 in Serum.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Activation of EIF4E by Aurora Kinase A Depicts a Novel Druggable Axis in Everolimus-Resistant Cancer Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsDopamine and adenosine 3',5'-cyclic monophosphate-regulated phosphoprotein, Mr 32000 (DARPP-32), is overexpressed during gastric carcinogenesis. Gastric tumors can become resistant to gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR). We investigated the role of DARPP-32 in gastric tumor resistance to gefitinib.
methodsCell survival was determined by clonogenic survival and ATP-Glo Viability Assays. Apoptosis was assessed by Annexin-V and immunoblot analyses. The association between DARPP-32 and EGFR was evaluated by immunofluorescence and co-immunoprecipitation assays. Findings were validated in mice with gastric xenograft tumors. DARPP-32 expression was reduced using small hairpin RNAs in the human gastric cancer cell lines SNU-16 and MKN-45 cells.
resultsOverexpression of DARPP-32 in MKN-28 cells, which do not normally express DARPP-32, blocked gefitinib-induced apoptosis and increased the drug's IC(50) 10-fold, compared to that of control cells (P < .01). Reduced expression of DARPP-32 in SNU-16 cells increased the sensitivity to gefitinib (P < .01). DARPP-32 activated phosphatidylinositol-3-kinase-AKT signaling, increased stability of the EGFR, and suppressed EGF- or gefitinib-induced degradation of the EGFR. DARPP-32 colocalized with EGFR on the cell membrane in a complex with EGFR and the EGF receptor ERBB3. DARPP-32-mediated resistance to gefitinib resulted from increased phosphorylation of and interaction between EGFR and ERBB3, which led to phosphorylation of AKT (at serine 473). Knockdown of DARPP-32 in gastric cancer cells reduced the mean size of tumors in mice and increased their response to gefitinib.
conclusionsDARPP-32 promotes resistance of gastric cancer cells to gefitinib by promoting interaction between EGFR and ERBB3 and activating phosphatidylinositol-3-kinase-AKT signaling.
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