ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Exploring STK3 in melanoma: a systematic review of signaling networks and therapeutic opportunities.Molecular biology reports · 2024Pooled it
- Structure-Based Virtual Screening andACS omega · 2026Article
- Article
- A soft-stiff patterned bioengineering model reveals kinase pathways driving directional cell migration in pulmonary arterial hypertension.Biomaterials science · 2025Article
- HOMER3 orchestrates SRC-YAP1 activity that promotes tumor cell growth and antagonizes anti-tumor immunotherapy in prostate cancer.Oncogene · 2025Article
- STK3 is a transcriptional target of YAP1 and a hub component in the crosstalk between Hippo and Wnt signaling pathways during gastric carcinogenesis.Molecular cancer · 2025Article
- Comparison of Differentially Expressed Genes in Human and Canine Osteosarcoma.Life (Basel, Switzerland) · 2025Article
- Decoding gene expression profiles of Hippo signaling pathway components in breast cancer.Molecular biology reports · 2025Article
- Functional annotation of the Hippo pathway somatic mutations in human cancers.Nature communications · 2024Article
- STK3 kinase activation inhibits tumor proliferation through FOXO1-TP53INP1/P21 pathway in esophageal squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- STK3 higher expression association with clinical characteristics in intrinsic subtypes of breast cancer invasive ductal carcinoma patients.Breast cancer research and treatment · 2024Article
- Drug Repurposing: Exploring Potential Anti-Cancer Strategies by Targeting Cancer Signalling Pathways.Biology · 2024Review
- Article
- The significance of Hippo pathway protein expression in oral squamous cell carcinoma.Frontiers in medicine · 2024Article
- Article
- The hippo kinases MST1/2 in cardiovascular and metabolic diseases: A promising therapeutic target option for pharmacotherapy.Acta pharmaceutica Sinica. B · 2023Review
- The Molecular Biology of Prostate Cancer Stem Cells: From the Past to the Future.International journal of molecular sciences · 2023Review
- Developing a Kinase Chemogenomic Set: Facilitating Investigation into Kinase Biology by Linking Phenotypes to Targets.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The Hippo signalling pathway and its implications in human health and diseases.Signal transduction and targeted therapy · 2022Review
- Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Serine/threonine kinase 3 (STK3) is an essential member of the highly conserved Hippo tumor suppressor pathway that regulates Yes-associated protein 1 (YAP1) and TAZ. STK3 and its paralog STK4 initiate a phosphorylation cascade that regulates YAP1/TAZ inhibition and degradation, which is important for regulated cell growth and organ size. Deregulation of this pathway leads to hyperactivation of YAP1 in various cancers. Counter to the canonical tumor suppression role of STK3, we report that in the context of prostate cancer (PC), STK3 has a pro-tumorigenic role. Our investigation started with the observation that STK3, but not STK4, is frequently amplified in PC. Additionally, high STK3 expression is associated with decreased overall survival and positively correlates with androgen receptor (AR) activity in metastatic castrate-resistant PC. XMU-MP-1, an STK3/4 inhibitor, slowed cell proliferation, spheroid growth, and Matrigel invasion in multiple models. Genetic depletion of STK3 decreased proliferation in several PC cell lines. In a syngeneic allograft model, STK3 loss slowed tumor growth kinetics in vivo, and biochemical analysis suggests a mitotic growth arrest phenotype. To further probe the role of STK3 in PC, we identified and validated a new set of selective STK3 inhibitors, with enhanced kinase selectivity relative to XMU-MP-1, that inhibited tumor spheroid growth and invasion. Consistent with the canonical role, inhibition of STK3 induced cardiomyocyte growth and had chemoprotective effects. Our results indicate that STK3 has a non-canonical role in PC progression and that inhibition of STK3 may have a therapeutic potential for PC that merits further investigation.
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Registered trials
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