ArticleCell cycle (Georgetown, Tex.)2018
AKT inhibitor MK-2206 sensitizes breast cancer cells to MLN4924, a first-in-class NEDD8-activating enzyme (NAE) inhibitor.
Article in Cell cycle (Georgetown, Tex.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- MicroRNA-1303 in cancer pathogenesis and therapy: clinical implications for biomarker development and targeted treatment strategies.Cancer cell international · 2025Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- High-density lipoprotein protects normotensive and hypertensive rats against ischemia-reperfusion injury through differential regulation of mTORC1 and mTORC2 signaling.Frontiers in pharmacology · 2024Article
- Endoxifen downregulates AKT phosphorylation through protein kinase C beta 1 inhibition in ERα+ breast cancer.NPJ breast cancer · 2023Article
- ATM inhibitor KU60019 synergistically sensitizes lung cancer cells to topoisomerase II poisons by multiple mechanisms.Scientific reports · 2023Article
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- The Absence of PTEN in Breast Cancer Is a Driver of MLN4924 Resistance.Frontiers in cell and developmental biology · 2021Article
- miR‑589‑3p sponged by the lncRNA TINCR inhibits the proliferation, migration and invasion and promotes the apoptosis of breast cancer cells by suppressing the Akt pathway via IGF1R.International journal of molecular medicine · 2020Article
- NEDDylation negatively regulates ERRβ expression to promote breast cancer tumorigenesis and progression.Cell death & disease · 2020Article
- Article
- MK2206 Enhances Cisplatin-Induced Cytotoxicity and Apoptosis in Testicular Cancer Through Akt Signaling Pathway Inhibition.Translational oncology · 2020Article
- 5-Aza-2'-deoxycytidine advances the epithelial-mesenchymal transition of breast cancer cells by demethylatingJournal of cell science · 2020Article
- Article
- SCFOncogenesis · 2020Article
- Cellular Plasticity in Breast Cancer Progression and Therapy.Frontiers in molecular biosciences · 2020Review
- Ubiquitin and ubiquitin-like molecules in DNA double strand break repair.Cell & bioscience · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer is a common type of cancer among female cancer patients and the main cause of cancer-related deaths. During the last decades, targeted therapies for breast cancer have been rapidly developing. Among them, MLN4924, a first-in-class NEDD8-activating enzyme (NAE) inhibitor, has performed antitumor activity by inactivating the cullin-RING ligases and causing the accumulation of their substrates to induce apoptosis in a number of studies. In this study, we found that MLN4924 activates the AKT pathway in both HER2-positive and triple-negative breast cancer (TNBC) cell lines. Given that AKT signaling is responsible for tumor progression and drug resistance in some types of cancers, we hypothesized that the AKT inhibitor may synergistically enhance the tumor suppression capability in breast cancer by MLN4924. To demonstrate the sensitizing effect, MK-2206 was chosen as the adjuvant treatment, and cell growth, migration and apoptosis were detected. The results showed that MLN4924 treatment inhibited cell growth and migration and induced apoptosis in both SK-BR3 and MDA-MB231 breast cancer cell lines. More importantly, the combined treatment of MLN4924 and MK-2206 indeed caused stronger cytotoxicity and inhibition of migration and a much higher induction of apoptosis compared with MLN4924 treatment alone. Our study provides the proof-of-concept evidence for strategic drug combination of MLN4924 with an AKT inhibitor for maximal killing of breast cancer cells via the enhancement of apoptosis.
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