Oncogenic KRAS Regulates Secretion of Extracellular Vesicles and Surface Membrane Charge via Regulation of Phosphatidylserine in Pancreatic Cancer.
10 affiliations
- 1Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas77030, United States.
- 2Department of Bioengineering, Rice University, Houston, Texas77005, United States.
- 3Department of Electrical and Computer Engineering, Rice University, Houston, Texas77005, United States.
- 4Department of Systems, Synthetic, and Physical Biology, Rice University, Houston, Texas77005, United States.
- 5Applied Physics Program, Rice University, Houston, Texas77005, United States.
- 6Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas77005, United States.
- 7Department of Surgery II, University of Witten/Herdecke, Helios University Hospital Wuppertal, 42283Wuppertal, Germany.
- 8Department of General, Visceral, and Transplant Surgery, Heidelberg University, Heidelberg University Hospital, 69120Heidelberg, Germany.
- 9Department of Neuroscience, Baylor College of Medicine, Houston, Texas77030, United States.
- 10Department of Pathology, The University of Texas Medical Branch, Galveston, Texas77555, United States.
Abstract
Extracellular vesicles (EVs) have the potential to be used as a liquid biopsy for cancer detection and treatment response assessment. Although the potential of EVs as disease-specific biomarkers has been promising, the rapid and specific enrichment of EVs from body fluids in a clinical setting remains challenging. To address this limitation, we developed a microfluidic electrophoresis (MEP) device for the label-free, charge-based enrichment of EVs from the serum of patients with pancreatic cancer (PaCa). We first validated the principle of charge-based cancer EV enrichment using cell-line-derived EVs, demonstrating that increased signaling through mutant Kirsten rat sarcoma viral oncogene homologue (KRAS), particularly KrasG12D, was associated with enhanced EV secretion and a shift toward more negative ζ-potential values. We then evaluated EVs derived from the serum of patients with PaCa to assess the clinical relevance and translational potential of the MEP platform. Further analyses identified phosphatidylserine and extraluminal DNA as part of the molecular determinants of the enhanced anionic nature of the PaCa-derived EVs. Overall, this proof-of-concept study introduces a promising microfluidic platform for enriching circulating cancer EVs with potential applications in the rapid detection of PaCa.
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BibTeX
@article{spezza2026oncogenic,
title = {{Oncogenic KRAS Regulates Secretion of Extracellular Vesicles and Surface Membrane Charge via Regulation of Phosphatidylserine in Pancreatic Cancer.}},
author = {Paul A Spezza and Kshipra S Kapoor and Beatrice P Pforr and Xin Luo and Kaira A Church and Martin M Bell and Bo Fan and Seoyun Kong and Elena V Ramirez and Yi-Lin Chen and Fernanda G Kugeratski and Sibani Lisa Biswal and Kathleen M McAndrews and Florian Gebauer and Christoph Kahlert and Jacob T Robinson and Raghu Kalluri},
journal = {ACS nano},
year = {2026},
month = sep,
doi = {10.1021/acsnano.6c08263},
url = {https://europepmc.org/article/MED/42915039},
note = {CC BY},
}
RIS
TY - JOUR
TI - Oncogenic KRAS Regulates Secretion of Extracellular Vesicles and Surface Membrane Charge via Regulation of Phosphatidylserine in Pancreatic Cancer.
AU - Paul A Spezza
AU - Kshipra S Kapoor
AU - Beatrice P Pforr
AU - Xin Luo
AU - Kaira A Church
AU - Martin M Bell
AU - Bo Fan
AU - Seoyun Kong
AU - Elena V Ramirez
AU - Yi-Lin Chen
AU - Fernanda G Kugeratski
AU - Sibani Lisa Biswal
AU - Kathleen M McAndrews
AU - Florian Gebauer
AU - Christoph Kahlert
AU - Jacob T Robinson
AU - Raghu Kalluri
PY - 2026
DA - 2026/09/01
JO - ACS nano
DO - 10.1021/acsnano.6c08263
UR - https://europepmc.org/article/MED/42915039
AB - Extracellular vesicles (EVs) have the potential to be used as a liquid biopsy for cancer detection and treatment response assessment. Although the potential of EVs as disease-specific biomarkers has been promising, the rapid and specific enrichment of EVs from body fluids in a clinical setting remains challenging. To address this limitation, we developed a microfluidic electrophoresis (MEP) device for the label-free, charge-based enrichment of EVs from the serum of patients with pancreatic cancer (PaCa). We first validated the principle of charge-based cancer EV enrichment using cell-line-derived EVs, demonstrating that increased signaling through mutant Kirsten rat sarcoma viral oncogene homologue (KRAS), particularly KrasG12D, was associated with enhanced EV secretion and a shift toward more negative ζ-potential values. We then evaluated EVs derived from the serum of patients with PaCa to assess the clinical relevance and translational potential of the MEP platform. Further analyses identified phosphatidylserine and extraluminal DNA as part of the molecular determinants of the enhanced anionic nature of the PaCa-derived EVs. Overall, this proof-of-concept study introduces a promising microfluidic platform for enriching circulating cancer EVs with potential applications in the rapid detection of PaCa.
SN - 1936-0851
SN - 1936-086X
ER -