ArticleMolecular cancer therapeutics2015
New Blocking Antibodies against Novel AGR2-C4.4A Pathway Reduce Growth and Metastasis of Pancreatic Tumors and Increase Survival in Mice.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- The prognostic value of AGR2 expression in solid tumours: a systematic review and meta-analysis.Scientific reports · 2017Pooled it
- Complementary intra- and extracellular AGR2 activities support epithelial ovarian cancer cell aggressiveness.Oncogene · 2026Article
- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- Article
- Agr2 in cancer and beyond: unraveling its role during protein synthesis, ER stress, and as a predictive biomarker.Molecular and cellular biochemistry · 2025Review
- Non-Canonical, Strongly Selective Protein Disulfide Isomerases as Anticancer Therapeutic Targets.Biomolecules · 2025Review
- Multi-omics and single-cell analysis reveals machine learning-based pyrimidine metabolism-related signature in the prognosis of patients with lung adenocarcinoma.International journal of medical sciences · 2025Article
- A High-Affinity Monoclonal Antibody Against the Pancreatic Ductal Adenocarcinoma Target, Anterior Gradient-2 (AGR2/PDIA17).Antibodies (Basel, Switzerland) · 2024Article
- Prevalence and Significance of AGR2 Expression in Human Cancer.Cancer medicine · 2024Article
- AGR2: The Covert Driver and New Dawn of Hepatobiliary and Pancreatic Cancer Treatment.Biomolecules · 2024Review
- AGR2-mediated unconventional secretion of 14-3-3ε and α-actinin-4, responsive to ER stress and autophagy, drives chemotaxis in canine mammary tumor cells.Cellular & molecular biology letters · 2024Article
- Review
- LY6/PLAUR domain containing 3 (LYPD3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment.Biology direct · 2023Article
- Anterior gradient 2 induces resistance to sorafenib via endoplasmic reticulum stress regulation in hepatocellular carcinoma.Cancer cell international · 2023Article
- AGR2: a secreted protein worthy of attention in diagnosis and treatment of breast cancer.Frontiers in oncology · 2023Review
- Transcriptomic analysis of pancreatic adenocarcinoma specimens obtained from Black and White patients.PloS one · 2023Article
- Anterior gradient proteins in gastrointestinal cancers: from cell biology to pathophysiology.Oncogene · 2022Review
- Inhibitory Effect of Etravirine, a Non-Nucleoside Reverse Transcriptase Inhibitor, via Anterior Gradient Protein 2 Homolog Degradation against Ovarian Cancer Metastasis.International journal of molecular sciences · 2022Article
- Monoclonal Antibodies Generation: Updates and Protocols on Hybridoma Technology.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Human endometrial cell-type-specific RNA sequencing provides new insights into the embryo-endometrium interplay.Human reproduction open · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Anterior gradient 2 (AGR2) promotes cancer growth, metastasis, and resistance to therapy via unknown mechanisms. We investigated the effects of extracellular AGR2 signaling through the orphan glycosylphosphatidylinositol-linked receptor C4.4A in pancreatic ductal adenocarcinoma (PDAC). Proliferation, migration, invasion, and apoptosis were measured using colorimetric, Boyden chamber, and FACS analyses. We developed blocking mAbs against AGR2 and C4.4A and tested their effects, along with siRNAs, on cancer cell functions and on orthotopic tumors in nude mice. Extracellular AGR2 stimulated proliferation, migration, invasion, and chemoresistance of PDAC cell lines. AGR2 interacted with C4.4A in cell lysates and mixtures of recombinant proteins. Knockdown of C4.4A reduced migration and resistance to gemcitabine. PDAC tissues, but not adjacent healthy pancreatic tissues, expressed high levels of AGR2 and C4.4A. AGR2 signaling through C4.4A required laminins 1 or 5 and integrin β1. Administration of antibodies against AGR2 and C4.4A reduced growth and metastasis and caused regression of aggressive xenograft tumors, leading to increased survival of mice. These data support a model in which AGR2 binds and signals via C4.4A in an autocrine loop and promotes the growth of pancreas tumors in mice. Blocking mAbs against AGR2 and C4.4A may have therapeutic potential against PDAC.
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