ArticleCell communication and signaling : CCS2020
Kinase shRNA screening reveals that TAOK3 enhances microtubule-targeted drug resistance of breast cancer cells via the NF-κB signaling pathway.
Article in Cell communication and signaling : CCS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 27 citations in OpenAlex.
- Mechanisms of Paclitaxel Resistance: Recent Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- Plasma Proteomics Identifies Thousand-and-One-Amino Acid Kinase 3 as a Potential Biomarker of Rheumatoid Arthritis Activity and a Novel Therapeutic Target.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- The Ste20 kinase TAOK3 restrains Rac-driven cytoskeletal-mitochondrial coupling to preserve naive CD8Frontiers in immunology · 2026Article
- Proteomic insights into breast cancer response to brain cell-secreted factors.Scientific reports · 2024Article
- Lck Function and Modulation: Immune Cytotoxic Response and Tumor Treatment More Than a Simple Event.Cancers · 2024Review
- The role of TAOK3 in cancer progression and development as a prognostic marker: A pan-cancer analysis study.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Knockout of STE20-type kinase TAOK3 does not attenuate diet-induced NAFLD development in mice.Molecular medicine (Cambridge, Mass.) · 2023Article
- TAOK3 Facilitates Esophageal Squamous Cell Carcinoma Progression and Cisplatin Resistance Through Augmenting Autophagy Mediated by IRGM.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- TAOK3 limits age-associated inflammation by negatively modulating macrophage differentiation and their production of TNFα.Immunity & ageing : I & A · 2023Article
- Cellular and Molecular Effects of Eribulin in Preclinical Models of Hematologic Neoplasms.Cancers · 2022Article
- Construction of PARPi Resistance-related Competing Endogenous RNA Network.Current genomics · 2022Article
- Polo-Like Kinase 1 Regulates Chromosomal Instability and Paclitaxel Resistance in Breast Cancer Cells.Journal of breast cancer · 2022Article
- Autophagy Blockade by Ai Du Qing Formula Promotes Chemosensitivity of Breast Cancer Stem Cells Via GRP78/β-Catenin/ABCG2 Axis.Frontiers in pharmacology · 2021Article
- The Diverse Roles of TAO Kinases in Health and Diseases.International journal of molecular sciences · 2020Review
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8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChemotherapy is currently one of the most effective treatments for advanced breast cancer. Anti-microtubule agents, including taxanes, eribulin and vinca-alkaloids are one of the primary major anti-breast cancer chemotherapies; however, chemoresistance remains a problem that is difficult to solve. We aimed to discover novel candidate protein targets to combat chemoresistance in breast cancer.
methodsA lentiviral shRNA-based high-throughput screening platform was designed and developed to screen the global kinome to find new therapeutic targets in paclitaxel-resistant breast cancer cells. The phenotypes were confirmed with alternative expression in vitro and in vivo. Molecular mechanisms were investigated using global phosphoprotein arrays and expression microarrays. Global microarray analysis was performed to determine TAOK3 and genes that induced paclitaxel resistance.
resultsA serine/threonine kinase gene, TAOK3, was identified from 724 screened kinase genes. TAOK3 shRNA exhibited the most significant reduction in IC50 values in response to paclitaxel treatment. Ectopic downregulation of TAOK3 resulted in paclitaxel-resistant breast cancer cells sensitize to paclitaxel treatment in vitro and in vivo. The expression of TAOK3 also was correlated to sensitivity to two other anti-microtubule drugs, eribulin and vinorelbine. Our TAOK3-modulated microarray analysis indicated that NF-κB signaling played a major upstream regulation role. TAOK3 inhibitor, CP43, and shRNA of NF-κB both reduced the paclitaxel resistance in TAOK3 overexpressed cells. In clinical microarray databases, high TAOK3 expressed breast cancer patients had poorer prognoses after adjuvant chemotherapy.
conclusionsHere we identified TAOK3 overexpression increased anti-microtubule drug resistance through upregulation of NF-κB signaling, which reduced cell death in breast cancer. Therefore, inhibition of the interaction between TAOK3 and NF-κB signaling may have therapeutic implications for breast cancer patients treated with anti-microtubule drugs. Video abstract.
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