ArticleMolecular cancer research : MCR2014
Targeting TBK1 inhibits migration and resistance to MEK inhibitors in mutant NRAS melanoma.
Article in Molecular cancer research : MCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Tumor microenvironment and signaling pathways in melanoma brain metastasis.Annals of translational medicine · 2026Review
- cGAS/STING signalling pathway in senescence and oncogenesis.Seminars in cancer biology · 2024Review
- Review
- TBK1 is paradoxical in tumor development: a focus on the pathway mediating IFN-I expression.Frontiers in immunology · 2024Review
- TargetingJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Efficient prioritization of CRISPR screen hits by accounting for targeting efficiency of guide RNA.BMC biology · 2023Article
- A Genome-Wide Screen Identifies PDPK1 as a Target to Enhance the Efficacy of MEK1/2 Inhibitors in NRAS Mutant Melanoma.Cancer research · 2022Article
- The role of TBK1 in cancer pathogenesis and anticancer immunity.Journal of experimental & clinical cancer research : CR · 2022Review
- Targeting IKKε in Androgen-Independent Prostate Cancer Causes Phenotypic Senescence and Genomic Instability.Molecular cancer therapeutics · 2022Article
- Choosing Kinase Inhibitors for Androgen Deprivation Therapy-Resistant Prostate Cancer.Pharmaceutics · 2022Review
- Employing CRISPR-Cas9 to Generate CD133 Synthetic Lethal Melanoma Stem Cells.International journal of molecular sciences · 2022Article
- Conquering oncogenic KRAS and its bypass mechanisms.Theranostics · 2022Review
- Knockdown of TANK-Binding Kinase 1 Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular-Targeted Drugs.Frontiers in pharmacology · 2022Article
- Inhibitory targeting cGAS-STING-TBK1 axis: Emerging strategies for autoimmune diseases therapy.Frontiers in immunology · 2022Review
- Mutational analysis and protein profiling predict drug sensitivity in multiple myeloma cell lines.Frontiers in oncology · 2022Article
- TBK1 Inhibitor Exerts Antiproliferative Effect on Glioblastoma Multiforme Cells.Oncology research · 2021Article
- Many Distinct Ways Lead to Drug Resistance inLife (Basel, Switzerland) · 2021Review
- TANK-Binding Kinase 1 (TBK1) Serves as a Potential Target for Hepatocellular Carcinoma by Enhancing Tumor Immune Infiltration.Frontiers in immunology · 2021Article
- Targeting PHGDH Upregulation Reduces Glutathione Levels and Resensitizes Resistant NRAS-Mutant Melanoma to MAPK Kinase Inhibition.The Journal of investigative dermatology · 2020Article
- Targeting TANK-binding kinase 1 (TBK1) in cancer.Expert opinion on therapeutic targets · 2020Review
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledMelanoma is a devastating form of skin cancer with limited therapeutic options. Fifteen to 20% of patients with melanoma have an activating mutation in the GTPase, NRAS. The major downstream effectors of RAS are RAFs (ARAF, BRAF, and CRAF), phosphoinositide 3-kinase (PI3K), and the Ral guanine exchange factors (RalGEF). TANK-binding kinase 1 (TBK1) is an atypical IκB kinase family member that acts downstream of RalGEFs. Whereas many studies have analyzed RAF and PI3K signaling in mutant NRAS melanoma, the role of RalGEF/Ral is understudied and TBK1 has not been examined. To address this, TBK1 was modulated with knockdown approaches and targeted therapies to determine the role of TBK1 in motility, apoptosis, and signaling. In melanoma, NRAS overexpression increased TBK1 phosphorylation. TBK1 depletion inhibited migration and invasion, whereas its constitutive overexpression led to an increase in invasion. In three-dimensional systems that mimic the dermal microenvironment, TBK1 depletion or inhibition cooperated with MEK inhibitors to promote apoptosis, particularly in the context of MEK-insensitive mutant NRAS. This effect was absent in melanoma cells that are wild-type for NRAS. These results suggest the utility of TBK1 inhibitors as part of a treatment regimen for patients with mutant NRAS melanoma, for whom there are no current effective therapies. IMPLICATIONS: TBK1 promotes the malignant properties of NRAS-mutant melanoma and its targeting, in combination with MEK, promotes apoptosis, thus providing a potential novel targeted therapeutic option.
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