ArticleCancer gene therapy2024
Neddylation of insulin receptor substrate acts as a bona fide regulator of insulin signaling and its implications for cancer cell migration.
Article in Cancer gene therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- IRS2 as a driver and therapeutic target in brain metastases from colorectal cancer: a systematic review of mechanistic and translational evidence.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Pooled it
- Neddylation as a molecular integrator of metabolic dysfunction and endothelial dysfunction in type 2 diabetes.Acta pharmacologica Sinica · 2026Review
- Adipocyte-Derived Palmitic Acid Promotes Breast Cancer Malignancy via ZDHHC15-Mediated S-Palmitoylation of PPARγ.Cancer science · 2026Article
- Paracrine signals from HIV-1-infected immune cells reprogram cervical cancer pathways.iScience · 2026Article
- Role of neddylation in diabetes metabolism: potential therapeutic target.Journal of diabetes and metabolic disorders · 2026Review
- Rewriting the MASLD-associated hepatocellular carcinoma script: Targeting epigenetics and metabolism.International journal of cancer · 2025Review
- Interconnected Mechanistic Pathways, Molecular Biomarkers, and Therapeutic Approach of Oral Cancer in Patients with Diabetes Mellitus.Current issues in molecular biology · 2025Review
- Disease-specific epigenetic deregulation of enhancers, transposons, and polycomb targets in acute promyelocytic leukemia.Genome medicine · 2025Article
- Celastrol modulates IRS1 expression to alleviate ovarian aging and to enhance follicular development.Cell biology and toxicology · 2025Article
- Unraveling the glyco-immunity nexus in pancreatic cancer.Molecular cancer · 2025Review
- Obesity-cancer axis crosstalk: Molecular insights and therapeutic approaches.Acta pharmaceutica Sinica. B · 2025Review
- Neddylation steers the fate of cellular receptors.Experimental & molecular medicine · 2024Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Irregularities in insulin signaling have significantly increased the risk of various cancers, yet the precise underlying mechanisms remain unclear. Within our study, we observed that inhibiting neddylation enhances cancer cell migration across different cancer types by activating both insulin receptor substrates 1 and 2 (IRS1 and IRS2), along with the PI3K/AKT signaling pathway. Notably, in the context of high-grade serous carcinoma (HGSC) patients, whether they had type 2 diabetes mellitus or not, IRS1 and IRS2 displayed a parallel relationship with each other while exhibiting an inverse relationship with NEDD8. We also identified C-CBL as an E3 ligase responsible for neddylating IRS1 and IRS2, with clinical evidence further confirming a reciprocal relationship between C-CBL and pAKT, thereby reinforcing the tumor suppressive role of C-CBL. Altogether, these findings suggest that neddylation genuinely participates in IRS1 and IRS2-dependent insulin signaling, effectively suppressing cancer cell migration. Thus, caution is advised when considering neddylation inhibitors as a treatment option for cancer patients, particularly those presenting with insulin signaling dysregulations linked to conditions like obesity-related type 2 diabetes or hyperinsulinemia.
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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.