ArticleMolecular cancer research : MCR2015
RNA-seq reveals aurora kinase-driven mTOR pathway activation in patients with sarcomatoid metastatic renal cell carcinoma.
Article in Molecular cancer research : MCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
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- MicroRNA Regulation of T-Cell Exhaustion in Cutaneous T Cell Lymphoma.The Journal of investigative dermatology · 2022Article
- Multiregion sequencing of sarcomatoid renal cell carcinoma arising from autosomal dominant polycystic kidney disease.Molecular genetics & genomic medicine · 2022Article
- A challenging frontier - the genomics and therapeutics of nonclear cell renal cell carcinoma.Current opinion in oncology · 2021Review
- The Aurora kinase/β-catenin axis contributes to dexamethasone resistance in leukemia.NPJ precision oncology · 2021Article
- AURKB as a Promising Prognostic Biomarker in Hepatocellular Carcinoma.Evolutionary bioinformatics online · 2021Article
- Circulating tumor DNA analysis of metastatic renal cell carcinoma.Molecular and clinical oncology · 2021Article
- Influence of gene expression on survival of clear cell renal cell carcinoma.Cancer medicine · 2020Article
- MYC-binding lncRNA EPIC1 promotes AKT-mTORC1 signaling and rapamycin resistance in breast and ovarian cancer.Molecular carcinogenesis · 2020Article
- Genomic profiling in renal cell carcinoma.Nature reviews. Nephrology · 2020Review
- Genetic Alterations in Renal Cancers: Identification of The Mechanisms Underlying Cancer Initiation and Progression and of Therapeutic Targets.Medicines (Basel, Switzerland) · 2020Review
- A miRNA- and mRNA-seq-Based Feature Selection Approach for Kidney Cancer Biomakers.Cancer informatics · 2020Article
- Sarcomatoid Dedifferentiation in Renal Cell Carcinoma: From Novel Molecular Insights to New Clinical Opportunities.Cancers · 2019Review
- Androgen Receptor and PI3K Pathway Activity in Ovarian Cancer.Journal of cancer research and therapeutic oncology · 2019Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledSarcomatoid metastatic renal cell carcinoma (mRCC) is associated with a poor prognosis, and the biology of the disease has been inadequately characterized. RNA sequencing (RNA-seq) was performed on adjacent benign, clear cell, and sarcomatoid components from clinical specimens with sarcomatoid mRCC. M phase and cell-cycle pathways were enriched in sarcomatoid versus adjacent clear cell components, suggesting greater cell proliferation. The expression of aurora kinase A (AURKA) was increased as part of these pathways, and its increased expression was validated by quantitative PCR (qPCR). Immunohistochemical (IHC) analysis revealed that AURKA levels were increased in sarcomatoid tissue compared with their benign or clear cell parts. The increase in AURKA correlated with increased mTOR pathway activity, as evidenced by increased expression of phosphorylated mTOR (S2448) and ribosomal protein S6K (T389). When AURKA was stably expressed in a RCC cell line (Renca), it resulted in increased expression and activity of mTOR, suggesting that overexpression of AURKA can activate the mTOR pathway. These results warrant the analysis of a larger clinical cohort and suggest that targeting AURKA and/or mTOR in patients with sarcomatoid mRCC should be explored. IMPLICATIONS: Comparative RNA-seq of adjacent sarcomatoid and clear cell histology of RCC indicates a proliferative phenotype and increased AURKA-dependent activation of mTOR signaling in sarcomatoid RCC, which could be targeted by available agents.
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