ArticleCancer letters2016
p-21 activated kinase 4 (PAK4) maintains stem cell-like phenotypes in pancreatic cancer cells through activation of STAT3 signaling.
Article in Cancer letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 84 citations in OpenAlex.
- The interplay between p21-activated kinases and tumour-infiltrating dendritic cells and T cells and its implication in pancreatic cancer immunotherapy.Cell communication and signaling : CCS · 2026Review
- The Effects of PAK-Regulated Tumour Vasculature on Gemcitabine Response of Pancreatic Cancer.Cancers · 2025Article
- PAK4 phosphorylates and stabilizes MYC to promote acute myeloid leukemia.Cell insight · 2025Article
- Multifaceted roles of OCT4 in tumor microenvironment: biology and therapeutic implications.Oncogene · 2025Review
- The Role of the p21-Activated Kinase Family in Tumor Immunity.International journal of molecular sciences · 2025Review
- Article
- METTL14 Suppresses Tumor Stemness and Metastasis of Colon Cancer Cells by Modulating m6A-Modified SCD1.Molecular biotechnology · 2024Article
- Elevated CDC45 Expression Predicts Poorer Overall Survival Prognoses and Worse Immune Responses for Kidney Renal Clear Cell Carcinoma via Single-Cell and Bulk RNA-Sequencing.Biochemical genetics · 2024Article
- Inhibition of P21-activated kinases 1 and 4 synergistically suppresses the growth of pancreatic cancer by stimulating anti-tumour immunity.Cell communication and signaling : CCS · 2024Article
- Targeting PAK4 reverses cisplatin resistance in NSCLC by modulating ER stress.Cell death discovery · 2024Article
- Review
- The Role of Krüppel-like Factors in Pancreatic Physiology and Pathophysiology.International journal of molecular sciences · 2023Review
- Cancer Stem Cells in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2023Review
- PAK4-relevant proliferation reduced by cell autophagy via p53/mTOR/p-AKT signaling.Translational cancer research · 2023Article
- Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity.Biomedicines · 2023Review
- Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside.Experimental hematology & oncology · 2022Review
- P21-Activated Kinase 4 Pak4 Maintains Embryonic Stem Cell Pluripotency via Akt Activation.Stem cells (Dayton, Ohio) · 2022Article
- Review
- p21-Activated kinases as promising therapeutic targets in hematological malignancies.Leukemia · 2022Review
- Resistin Induces LIN28A-Mediated Let-7a Repression in Breast Cancer Cells Leading to IL-6 and STAT3 Upregulation.Cancers · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Pancreatic cancer (PC) remains a highly lethal malignancy due to its unusual chemoresistance and high aggressiveness. A subpopulation of pancreatic tumor cells, known as cancer stem cells (CSCs), is considered responsible not only for tumor-maintenance, but also for its widespread metastasis and therapeutic failure. Here we investigated the role of p-21 activated kinase 4 (PAK4) in driving PC stemness properties. Our data demonstrate that triple-positive (CD24(+)/CD44(+)/EpCAM(+)) subpopulation of pancreatic CSCs exhibits greater level of PAK4 as compared to triple-negative (CD24(-)/CD44(-)/EpCAM(-)) cells. Moreover, PAK4 silencing in PC cells leads to diminished fraction of CD24, CD44, and EpCAM positive cells. Furthermore, we show that PAK4-silenced PC cells exhibit decreased sphere-forming ability and increased chemosensitivity to gemcitabine toxicity. PAK4 expression is also associated with enhanced levels of stemness-associated transcription factors (Oct4/Nanog/Sox2 and KLF4). Furthermore, our data show decreased nuclear accumulation and transcriptional activity of STAT3 in PAK4-silenced PC cells and restitution of its activity leads to restoration of stem cell phenotypes. Together, our findings deliver first experimental evidence for the involvement of PAK4 in PC stemness and support its clinical utility as a novel therapeutic target in PC.
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Registered trials
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