ORIGINAL RESEARCH article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1631350
Significance of FXa and its receptor PAR2 for the growth of colon cancer cells in vitro and in vivo
Provisionally accepted
Ulrike Meyer1*
Vincent Rönnpagel2Sophie Grammbauer2Mirjam von Lucadou3Ursula Rauch-Kröhnert4
Edzard Schwedhelm3
Frank Dombrowski2Christoph Ritter5
Bernhard H. Rauch6- 1University of Oldenburg, Oldenburg, Germany
- 2University Medicine Greifswald, Greifswald, Germany
- 3University Medical Center Eppendorf, Hamburg, Germany
- 4German Heart Center of Charité, Berlin, Germany
- 5University Greifswald, Greifswald, Germany
- 6University Oldenburg, Oldenburg, Germany
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Colon cancer is among the most common cancer types worldwide. Signaling pathways that control cell proliferation and migration play a crucial role in its progression. The G-protein-coupled protease-activated receptors (PARs) are associated mediators in this process. Both activated coagulation factors thrombin and FXa are capable of activating PARs. While thrombin, beyond its intrinsic role in hemostasis, primarily activates PAR1, FXa mediates its cellular effects independently via PAR2. Although the role of thrombin and PAR1 activation in cancer development has been established for some time, the impact of FXa-PAR2 on tumor progression represents a relatively novel area of investigation. As cancer is associated with an activated coagulation and therefore FXa, the effects of PAR2 may have been underestimated to date. Therefore, the current study was conducted to examine the correlation between tumor progression and PAR2 signaling using the murine colon cancer cell line MC38. The findings demonstrate that FXa considerably augments the proliferation and migration of colon cancer (CC) cells in vitro. A molecular mechanism of action has been identified in the activation of PAR2 by FXa. The coagulation factor significantly induces MAPK- and AKT-signaling with EGFR transactivation in the murine MC38 cells utilized. Although oral treatment with a direct FXa inhibitor (Apixaban) at a dosage of up to 50 mg/kg did not significantly affect tumor growth in vivo, PAR2 deficiency resulted in significantly reduced tumor growth and enhanced health condition status, indicating a key role of PAR2 in the progression of colon cancer.
Keywords: mouse model, Colon Cancer, PAR2 in colon cancer, FXa in colon cancer, in vivo study
Received: 28 May 2025; Accepted: 25 Jun 2025.
Copyright: © 2025 Meyer, Rönnpagel, Grammbauer, von Lucadou, Rauch-Kröhnert, Schwedhelm, Dombrowski, Ritter and Rauch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ulrike Meyer, University of Oldenburg, Oldenburg, Germany
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.