ArticleOncogene2020
Therapeutically actionable PAK4 is amplified, overexpressed, and involved in bladder cancer progression.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Novel Functionalized Pyrrolopyridines to Target Brk.Molecules (Basel, Switzerland) · 2026Article
- Elevated PTK6 expression is associated with tumor immune microenvironment remodeling and predicts poor prognosis in endometrial carcinoma.Frontiers in medicine · 2026Article
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- Urothelial collective-gliding response acts as a toll-like receptor 4-associated defense mechanism.iScience · 2025Article
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- The Role of the p21-Activated Kinase Family in Tumor Immunity.International journal of molecular sciences · 2025Review
- Design, synthesis and pharmacological evaluation of 1,2,3,4-tetrahydrobenzofuro[2,3-Acta pharmaceutica Sinica. B · 2025Article
- Inhibition of Erb-B2 Receptor Tyrosine Kinase 3 and Associated Regulatory Pathways Potently Impairs Malignant Peripheral Nerve Sheath Tumor Proliferation and Survival.The American journal of pathology · 2023Article
- Circ_0000235 targets MCT4 to promote glycolysis and progression of bladder cancer by sponging miR-330-5p.Cell death discovery · 2023Article
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- Using cancer proteomics data to identify gene candidates for therapeutic targeting.Oncotarget · 2023Article
- LncRNA IGFL2-AS1 as a ceRNA Promotes HCT116 Cell Malignant Proliferation via the miR-433-3p/PAK4 Axis.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2023Article
- The role of p21-activated kinase 4 in the progression of oral squamous cell carcinoma by targeting PI3K-AKT signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Remodeling of the tumor microenvironment through PAK4 inhibition sensitizes tumors to immune checkpoint blockade.Cancer research communications · 2022Article
- Prognostic value and potential biological functions of ferroptosis-related gene signature in bladder cancer.Oncology letters · 2022Article
- An in vivo model of glioblastoma radiation resistance identifies long noncoding RNAs and targetable kinases.JCI insight · 2022Article
- ARID1A-deficient bladder cancer is dependent on PI3K signaling and sensitive to EZH2 and PI3K inhibitors.JCI insight · 2022Article
- Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder.Biomedicines · 2022Review
- HSPB8 is a Potential Prognostic Biomarker that Correlates With Immune Cell Infiltration in Bladder Cancer.Frontiers in genetics · 2022Article
- Interfering with pak4 Protein Expression Affects Osteosarcoma Cell Proliferation and Migration.BioMed research international · 2021Article
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26 authors at 5 institutions in 2 countries.
Funding
Abstract
Muscle-invasive bladder carcinomas (MIBCs) are aggressive genitourinary malignancies. Metastatic urothelial carcinoma of the bladder is generally incurable by current chemotherapy and leads to early mortality. Recent studies have identified molecular subtypes of MIBCs with different sensitivities to frontline therapy, suggesting tumor heterogeneity. We have performed multi-omic profiling of the kinome in bladder cancer patients with the goal of identify therapeutic targets. Our analyses revealed amplification, overexpression, and elevated kinase activity of P21 (RAC1) activated kinase 4 (PAK4) in a subset of Bladder cancer (BLCA). Using bladder cancer cells, we confirmed the role of PAK4 in BLCA cell proliferation and invasion. Furthermore, we observed that a PAK4 inhibitor was effective in curtailing growth of BLCA cells. Transcriptomic analyses identified elevated expression of another kinase, protein tyrosine kinase 6 (PTK6), upon treatment with a PAK4 inhibitor and RNA interference of PAK4. Treatment with a combination of kinase inhibitors (vandetanib and dasatinib) showed enhanced sensitivity compared with either drug alone. Thus, PAK4 may be therapeutically actionable for a subset of MIBC patients with amplified and/or overexpressed PAK4 in their tumors. Our results also indicate that combined inhibition of PAK4 and PTK6 may overcome resistance to PAK4. These observations warrant clinical investigations with selected BLCA patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.