ArticleOncogene2019
Proteasome inhibition boosts autophagic degradation of ubiquitinated-AGR2 and enhances the antitumor efficiency of bevacizumab.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 83 citations in OpenAlex.
- Salicylic acid modulates its catabolic enzymes via proteasomal degradation linked to SCF-associated proximity networks.Nature communications · 2026Article
- PHIP suppresses NuRD to enable the growth of SWI/SNF-mutant cancers.Nature communications · 2026Article
- Regulation of STK38 by autophagy governs YAP1 activity during paligenosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Agr2 in cancer and beyond: unraveling its role during protein synthesis, ER stress, and as a predictive biomarker.Molecular and cellular biochemistry · 2025Review
- A BioID-based approach uncovers the interactome of hexose-6-phosphate dehydrogenase in breast cancer cells and identifies anterior gradient protein 2 as an interacting partner.Cell & bioscience · 2025Article
- Proteasome inhibitor MG132 modulates signal transduction pathways in ELT3 uterine leiomyoma cells.Experimental and therapeutic medicine · 2025Article
- Proteasome inhibition induces DNA methylation alteration by attenuating the synthesis of DNA methyltransferase 1 and 3B in colorectal cancer.Scientific reports · 2025Article
- Human cytomegalovirus UL82 promotes cell cycle progression of colorectal cancer by upregulating AGR2.Communications biology · 2025Article
- Angiogenesis is limited by LIC1-mediated lysosomal trafficking.Angiogenesis · 2024Article
- Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.Journal of translational medicine · 2024Review
- Article
- Inhibition of the ubiquitin-proteasome system reduces the abundance of pyruvate dehydrogenase kinase 1 in cultured myotubes.Journal of muscle research and cell motility · 2024Article
- HaloTag as a substrate-based macroautophagy reporter.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mitochondria-Targeted Oligomeric α-Synuclein Induces TOM40 Degradation and Mitochondrial Dysfunction in Parkinson's Disease and Parkinsonism-Dementia of Guam.Research square · 2024Article
- Itraconazole Confers Cytoprotection Against Neurodegenerative Disease-Associated Abnormal Protein Aggregation.Molecular neurobiology · 2023Article
- AGR2: a secreted protein worthy of attention in diagnosis and treatment of breast cancer.Frontiers in oncology · 2023Review
- Regulation of Epstein-Barr Virus Minor Capsid Protein BORF1 by TRIM5α.International journal of molecular sciences · 2022Article
- AGR2-induced cholesterol synthesis drives lovastatin resistance that is overcome by combination therapy with allicin.Acta pharmacologica Sinica · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anterior gradient 2 (AGR2), a protein belonging to the protein disulfide isomerase (PDI) family, is overexpressed in multiple cancers and promotes angiogenesis to drive cancer progression. The mechanisms controlling AGR2 abundance in cancer remain largely unknown. Here, we observed that AGR2 expression is significantly suppressed by proteasome inhibitor MG132/bortezomib at mRNA and protein levels in lung cancer cells. MG132-mediated repression of AGR2 transcription was independent of ROS generation and ER stress induction, but partially resulted from the downregulated E2F1. Further investigation revealed that MG132 facilitated polyubiquitinated AGR2 degradation through activation of autophagy, as evidenced by predominant restoration of AGR2 level in cells genetic depletion of Atg5 and Atg7, or by autophagy inhibitors. Activation of autophagy by rapamycin noticeably reduced the AGR2 protein in cells and in the mouse tissue samples administrated with bortezomib. We also provided evidence identifying the K48-linked polyubiquitin chains conjugating onto K89 of AGR2 by an E3 ligase UBR5. In addition, an autophagy receptor NBR1 was demonstrated to be important in polyubiquitinated AGR2 clearance in response to MG132 or bortezomib. Importantly, downregulation of AGR2 by proteasome inhibition significantly enhanced antitumor activity of bevacizumab, highlighting the importance of AGR2 as a predictive marker for selection of subgroup patients in chemotherapy.
Indexed as
Identifiers
What Socratic 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 Socratic graph.