ArticleGastroenterology2019
Inhibition of AURKA Reduces Proliferation and Survival of Gastrointestinal Cancer Cells With Activated KRAS by Preventing Activation of RPS6KB1.
Article in Gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 87 citations in OpenAlex.
- High Expression of Aurora Kinase A (AURKA) is Associated with Aggressive Tumor Biology and Therapeutic Response in ER+/HER2- Breast Cancer.Annals of surgical oncology · 2026Article
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- AURKA regulates LGR5 in response to Helicobacter Pylori infection by modulating its deubiquitination.Cell death and differentiation · 2026Article
- Aurora-A drives sorafenib resistance by scaffolding stress granule assembly via phase separation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- TCHP drives hepatocarcinogenesis through LLPS-mediated AURKA condensation and enables synergistic therapy.Cell death & disease · 2026Article
- NRF1 Transcriptionally Regulates USP1-Mediated Deubiquitination of AURKA to Facilitate Osteosarcoma Progression.Molecular biotechnology · 2026Article
- Proteomics and phosphoproteomics of human colorectal cancer cells lacking a specific kinase activity reveal kinase-specific compensatory responses.Animal cells and systems · 2026Article
- Aurora kinase A promotes trained immunity via regulation of endogenous S-adenosylmethionine metabolism.eLife · 2025Article
- Decoding hepatobiliary-specific immune gene patterns in gastrointestinal cancers via gene ontology fingerprints, multi-omics, and experimental integration.Precision clinical medicine · 2025Article
- A narrative review of papillary thyroid carcinoma-related long non-coding RNAs and their relevance to malignant tumors.Translational cancer research · 2025Review
- Identification of glycolysis-related gene signatures for prognosis and therapeutic targeting in idiopathic pulmonary fibrosis.Frontiers in pharmacology · 2025Article
- Proteogenomic characterization of skull-base chordoma.Nature communications · 2024Article
- The significant others of aurora kinase a in cancer: combination is the key.Biomarker research · 2024Review
- Adenovirus vaccine targeting kinases induces potent antitumor immunity in solid tumors.Journal for immunotherapy of cancer · 2024Article
- SOX9 is regulated by AURKA in response to Helicobacter pylori infection via EIF4E-mediated cap-dependent translation.Cancer letters · 2024Article
- Neutralizing IL-16 enhances the efficacy of targeting Aurora-A therapy in colorectal cancer with high lymphocyte infiltration through restoring anti-tumor immunity.Cell death & disease · 2024Article
- Aurora Kinase A: Integrating Insights into Cancer, Inflammation, and Infectious Diseases.Gut microbes reports · 2024Review
- Recent Updates on Oncogenic Signaling of Aurora Kinases in Chemosensitive, Chemoresistant Cancers: Novel Medicinal Chemistry Approaches for Targeting Aurora Kinases.Current medicinal chemistry · 2024Review
- Integration of proteomics and transcriptomics to construct a prognostic signature of renal clear cell carcinoma.International journal of medical sciences · 2024Article
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11 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsActivation of KRAS signaling and overexpression of the aurora kinase A (AURKA) are often detected in luminal gastrointestinal cancers. We investigated regulation of ribosomal protein S6 kinase B1 (RPS6KB1) by AURKA and the effects of alisertib, an AURKA inhibitor, in mice xenograft tumors grown from human gastrointestinal cancer cells with mutant, activated forms of KRAS.
methodsWe tested the effects of alisertib or AURKA overexpression or knockdown in 10 upper gastrointestinal or colon cancer cell lines with KRAS mutations or amplifications using the CellTiter-Glo luminescence and clonogenic cell survival assays. We used the proximity ligation in situ assay to evaluate protein co-localization and immunoprecipitation to study protein interactions. Nude mice with xenograft tumors grown from HCT116, SNU-601, SW480, or SNU-1 cells were given oral alisertib (40 mg/kg, 5 times/wk) for 4 weeks. Tumor samples were collected and analyzed by immunoblots and immunohistochemistry. Tissue microarrays from 151 paraffin-embedded human colon tumors, with adjacent normal and adenoma tissues, were analyzed by immunohistochemistry for levels of AURKA.
resultsAlisertib reduced proliferation and survival of the cell lines tested. AURKA knockdown or inhibition with alisertib reduced levels of phosphorylated RPS6KB1 (at T389) and increased levels of proteins that induce apoptosis, including BIM, cleaved PARP, and cleaved caspase 3. AURKA co-localized and interacted with RPS6KB1, mediating RPS6KB1 phosphorylation at T389. We detected AURKA-dependent phosphorylation of RPS6KB1 in cell lines with mutations in KRAS but not in cells with wild-type KRAS. Administration of alisertib to mice with xenograft tumors significantly reduced tumor volumes (P < .001). Alisertib reduced phosphorylation of RPS6KB1 and Ki-67 and increased levels of cleaved caspase 3 in tumor tissues. In analyses of tissue microarrays, we found significant overexpression of AURKA in gastrointestinal tumor tissues compared with non-tumor tissues (P = .0003).
conclusionIn studies of gastrointestinal cancer cell lines with activated KRAS, we found AURKA to phosphorylate RPS6KB1, promoting cell proliferation and survival and growth of xenograft tumors in mice. Agents that inhibit AURKA might slow the growth of gastrointestinal tumors with activation of KRAS.
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