ArticleOncotarget2016
Adrenomedullin blockade suppresses sunitinib-resistant renal cell carcinoma growth by targeting the ERK/MAPK pathway.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Retraction: MiR-506 Is Down-Regulated in Clear Cell Renal Cell Carcinoma and Inhibits Cell Growth and Metastasis via Targeting FLOT1.PloS one · 2026Article
- A Stable RNA Vaccine Against the Regulatory Peptide Adrenomedullin Reduces Angiogenesis and Tumor Burden in a Subcutaneous Melanoma Model Without Inducing an Immunosuppressive Tumor Microenvironment.International journal of molecular sciences · 2025Article
- Adrenomedullin in Tumorigenesis and Cancer Progression.International journal of molecular sciences · 2025Review
- Article
- IFITM3-mediated activation of TRAF6/MAPK/AP-1 pathways induces acquired TKI resistance in clear cell renal cell carcinoma.Investigative and clinical urology · 2024Article
- Peptidergic Systems and Cancer: Focus on Tachykinin and Calcitonin/Calcitonin Gene-Related Peptide Families.Cancers · 2023Review
- Protective effect of adrenomedullin on hyperoxia-induced lung injury.Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2021Article
- G6PD facilitates clear cell renal cell carcinoma invasion by enhancing MMP2 expression through ROS‑MAPK axis pathway.International journal of oncology · 2020Article
- ZHX2 drives cell growth and migration via activating MEK/ERK signal and induces Sunitinib resistance by regulating the autophagy in clear cell Renal Cell Carcinoma.Cell death & disease · 2020Article
- Targeting Adrenomedullin in Oncology: A Feasible Strategy With Potential as Much More Than an Alternative Anti-Angiogenic Therapy.Frontiers in oncology · 2020Review
- Oncogenic effects of RAB27B through exosome independent function in renal cell carcinoma including sunitinib-resistant.PloS one · 2020Article
- Computational identification and analysis of early diagnostic biomarkers for kidney cancer.Journal of human genetics · 2019Article
- The underlying molecular mechanism and potential drugs for treatment in papillary renal cell carcinoma: A study based on TCGA and Cmap datasets.Oncology reports · 2019Article
- Article
- JMJD1A, H3K9me1, H3K9me2 and ADM expression as prognostic markers in oral and oropharyngeal squamous cell carcinoma.PloS one · 2018Article
- Early and late effects of pharmacological ALK inhibition on the neuroblastoma transcriptome.Oncotarget · 2017Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo evaluate the mechanisms underlying sunitinib resistance in RCC and to identify targets that may be used to overcome this resistance.
resultsReanalysis of transcriptome microarray datasets (GSE64052 and GSE76068) showed that adrenomedullin expression was increased in sunitinib-resistant tumors. And adrenomedullin expression was increased in sunitinib-resistant tumor xenografts, accompanied by upregulation of phospho-ERK levels. However, blocking adrenomedullin inhibited sunitinib-resistant tumor growth. Treatment of RCC cells with sunitinib and ADM22-52 was superior to monotherapy with either agent. Additionally, adrenomedullin upregulated cAMP and activated the ERK/MAPK pathway, promoting cell proliferation, while knockdown of adrenomedullin inhibited RCC cell growth and invasion in vitro. MATERIALS AND
methodsWe searched the Gene Expression Omnibus (GEO) database to find data regarding sunitinib-resistant RCC. These data were subsequently reanalyzed to identify targets that contribute to sunitinib resistance, and adrenomedullin upregulation was found to mediate sunitinib resistance in RCC. Then, we created an RCC mouse xenograft model. Mice were treated with sunitinib, an adrenomedullin receptor antagonist (ADM22-52), a MEK inhibitor (PD98059) and different combinations of these three drugs to investigate their effects on tumor growth. RCC cells (786-0) were cultured in vitro and treated with an ADM22-52 or PD98059 to determine whether adrenomedullin activates the ERK/MAPK pathway. Adrenomedullin was knocked down in 786-0 cells via siRNA, and the effects of this knockdown on cell were subsequently investigated.
conclusionsAdrenomedullin plays an important role in RCC resistance to sunitinib treatment. The combination of sunitinib and an adrenomedullin receptor antagonist may result in better outcomes in advanced RCC patients.
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