ArticleOncotarget2017
Activated-PAK4 predicts worse prognosis in breast cancer and promotes tumorigenesis through activation of PI3K/AKT signaling.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- Cytoskeletal dynamics in breast cancer: mechanistic insights and therapeutic opportunities.Journal of the National Cancer Center · 2026Review
- Phosphoproteomic Profiling Identifies PAK4 S474 Phosphorylation Affects Docetaxel Chemosensitivity via Modulation of Microtubule Stabilization in Breast Cancer.Biomedicines · 2026Article
- Investigating PAK inhibition in combination with PD-1 blockade to enhance cytotoxic CD8+ T cell-mediated killing and suppress invasion of ovarian cancer cells.British journal of cancer · 2026Article
- A Spatiotemporal Model of CXCL10 as a Master Regulator of Immune Evasion and Metastasis in Osteosarcoma.International journal of molecular sciences · 2025Review
- P21-activated kinase 4: a potent oncogene, molecular mechanisms and opportunities for targeted therapy.Cancer cell international · 2025Review
- Review
- Increased SLC7A3 Expression Inhibits Tumor Cell Proliferation and Predicts a Favorable Prognosis in Breast Cancer.Recent patents on anti-cancer drug discovery · 2025Article
- Inhibition of NAMPT by PAK4 Inhibitors.International journal of molecular sciences · 2024Article
- PAK4 inhibition augments anti-tumour effect by immunomodulation in oral squamous cell carcinoma.Scientific reports · 2024Article
- Expression Patterns of PAK4 and PHF8 Are Associated with the Survival of Gallbladder Carcinoma Patients.Diagnostics (Basel, Switzerland) · 2023Article
- Pancreatic cancer and exosomes: role in progression, diagnosis, monitoring, and treatment.Frontiers in oncology · 2023Review
- Extracellular vesicles: Emerging tools as therapeutic agent carriers.Acta pharmaceutica Sinica. B · 2022Review
- Remodeling of the tumor microenvironment through PAK4 inhibition sensitizes tumors to immune checkpoint blockade.Cancer research communications · 2022Article
- Review
- Targeting of p21-Activated Kinase 4 Radiosensitizes Glioblastoma Cells via Impaired DNA Repair.Cells · 2022Article
- CORO1C, a novel PAK4 binding protein, recruits phospho-PAK4 at serine 99 to the leading edge and promotes the migration of gastric cancer cells.Acta biochimica et biophysica Sinica · 2022Article
- p21-Activated kinases as promising therapeutic targets in hematological malignancies.Leukemia · 2022Review
- Exosomes: the key of sophisticated cell-cell communication and targeted metastasis in pancreatic cancer.Cell communication and signaling : CCS · 2022Review
- Long non-coding RNA LINC01296 promotes progression of oral squamous cell carcinoma through activating the MAPK/ERK signaling pathway via the miR-485-5p/PAK4 axis.Archives of medical science : AMS · 2022Article
- Risk-Related Genes and Associated Signaling Pathways of Gastrointestinal Stromal Tumors.International journal of general medicine · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p21-activated kinase 4 (PAK4) is sufficient to transform noncancerous mammary epithelial cells and to form tumors in the mammary glands of mice. The accumulated information suggests that PAK4 might be an oncogenic protein in breast cancer. In this study, we sought to identify the role for PAK4 in breast cancer progression. Immunohistochemical study revealed that high PAK4 expression is associated with larger tumor size, lymph node metastasis, and advanced stage cancer in 93 invasive breast carcinoma patients. Moreover, high PAK4 expression was significantly associated with poor overall and disease-free survival. PAK4 remained an independent adverse prognosticator after univariate and multivariate analysis. Ectopic expression of wild-type PAK4 in MDA-MB-231 cells activated PI3K/AKT signaling and resulted in the enhancement of the cell proliferation, migration, and invasion, whereas PAK4-induced effects were blocked by the PAK4 kinase inhibitor PF- 3758309, PAK4 siRNAs or the PI3K inhibitor LY294002. Furthermore, a kinase-active PAK4 (S474E) strongly induced PI3K/AKT activation, and promoted proliferation, migration and invasion in breast cancer cells. A kinase-inactive PAK4 KD (K350A/K351A) did partially upregulate PI3K/AKT, and promoted invasive phenotype. Taken together, these findings suggest that PAK4-activated PI3K/AKT signaling is both kinase-dependent and -independent, which contributes to breast cancer progression. Thus, our results imply that dual inhibition of PAK4 and PI3K/AKT signaling might be a potential therapeutic approach for breast cancer therapy.
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