Related Experiment Video

Updated: Jan 18, 2026

Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
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Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma

Published on: November 19, 2019

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P-21 Kinase 1 or 4 Knockout Stimulated Anti-Tumour Immunity Against Pancreatic Cancer by Enhancing Vascular

Arian Ansardamavandi1, Chelsea Dumesny1, Yi Ma1,2

  • 1Department of Surgery, Austin Precinct, The University of Melbourne, 145 Studley Rd, Heidelberg, VIC 3084, Australia.

International Journal of Molecular Sciences
|September 13, 2025
PubMed

Insights

Targeting P-21-activated kinase 1 (PAK1) and PAK4 in pancreatic ductal adenocarcinoma (PDA) suppresses tumor growth. This involves normalizing tumor vasculature and boosting anti-tumor immune cell activity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Pancreatic ductal adenocarcinoma (PDA) is aggressive with poor survival due to molecular changes.
  • P-21-activated kinase 1 (PAK1) and PAK4 are key drivers of PDA tumorigenesis.
  • The roles of PAK1 and PAK4 in PDA tumor vasculature and immune response are not well understood.

Purpose of the Study:

  • To investigate the effects of PAK1 and PAK4 on PDA tumor vasculature.
  • To determine their impact on immune cell infiltration and activation.
  • To explore the connection between PAK1/PAK4 knockout and tumor progression.

Main Methods:

  • Utilized PAK1-knockout (KO), PAK4 KO, and wild-type (WT) PDA cells in cell-based and mouse models.
  • Performed immunohistochemistry on tumor tissues to analyze vasculature and immune cell changes.
  • Conducted proteomic studies to assess biological processes and molecular mechanisms.

Main Results:

  • PAK1 KO or PAK4 KO suppressed tumor growth by reducing angiogenesis and improving vascular normalization.
  • Enhanced infiltration and activation of T-cells and dendritic cells were observed.
  • Upregulation of ICAM-1 and VCAM-1 in the tumor microenvironment stimulated vascular immune crosstalk via an ICAM-1-mediated mechanism.

Conclusions:

  • PAK1 and PAK4 inhibition promotes tumor vascular normalization and reduces angiogenesis.
  • Knocking out PAK1 or PAK4 enhances anti-tumor immune cell infiltration and activation.
  • Targeting PAK1/PAK4 presents a potential therapeutic strategy for pancreatic cancer.
Keywords:
PAK1PAK4immune activationpancreatic ductal adenocarcinoma (PDA)vascular normalisation

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