Report
The kinase domain of TRPM7 interacts with PAK1 and regulates pancreatic cancer cell epithelial-to-mesenchymal transition
| العنوان: | The kinase domain of TRPM7 interacts with PAK1 and regulates pancreatic cancer cell epithelial-to-mesenchymal transition |
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| المؤلفون: | Gautier, Mathieu, Auwercx, Julie, Neve, Bernadette, Vanlaeys, Alison, Bourrin-Reynard, Ingrid, Soudi, Mouloud, Brassart-Pasco, Sylvie, Hague, Frédéric, Guénin, Stéphanie, Duchene, Belinda, Gutierrez, Laurent, Destaing, Olivier, Dhennin-Duthille, Isabelle, Seuningen, Isabelle Van, Jonckheere, Nicolas |
| المساهمون: | Laboratoire de Physiologie Cellulaire et Moléculaire - UR UPJV 4667 (LPCM), Université de Picardie Jules Verne (UPJV), Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Matrice Extracellulaire et Dynamique Cellulaire - UMR CNRS 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Centre de ressources régionales en biologie moléculaire - UPJV (CRRBM), Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 (MSAP), Institut de Chimie - CNRS Chimie (INC-CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | https://u-picardie.hal.science/hal-04882162 ; 2025. |
| بيانات النشر: | CCSD |
| سنة النشر: | 2025 |
| مصطلحات موضوعية: | PDAC, TRPM7, kinase domain, PAK1, EMT, [SDV.CAN]Life Sciences [q-bio]/Cancer |
| الوصف: | Pancreatic ductal adenocarcinoma (PDAC) is the main and the deadliest form of pancreatic cancer. This is a major problem of public health since it will become the second leading cause of death by cancer in the next few years, mainly due to the lack of efficient therapies. Transient Receptor Potential Cation Channel Subfamily M Member 7 (TRPM7) protein, a cation channel fused with a serine/threonine kinase domain is overexpressed in PDAC and associated with a low survival. In this work, we aim to study the role of kinase domain on pancreatic cell fates by using a model of kinase domain deletion by CRISPR-Cas9. PANC-1 and MIA PaCa-2 PDAC cell lines were used and kinase domain was deleted by CRISPR-Cas9 strategy. Kinase domain deletion (ΔK) was validated by RT-qPCR and western-blots. The effect of kinase domain deletion on channel function was studied by patch-clamp and Mn 2+ -quenching. The cell phenotype was studied by MTT and cell migration/invasion assays. Finally, the role of kinase domain was studied in vivo in xenografted mice. Here we show that TRPM7 kinase domain is required to maintain a mesenchymal phenotype in PDAC cells. We also demonstrated that TRPM7 and PAK1 interact in the same protein complexes. Moreover, TRPM7 kinase domain is required for carcinogenesis and cancer cell dissemination in vivo . Intriguingly, the role of TRPM7 kinase is cell specific and may depend on the KRAS oncogene mutation status. In conclusion, TRPM7 kinase domain is required to maintain a mesenchymal and aggressive phenotype in PDAC cells, and it could be a promising target against PDAC. |
| نوع الوثيقة: | report |
| اللغة: | English |
| DOI: | 10.21203/rs.3.rs-5549603/v1 |
| الاتاحة: | https://u-picardie.hal.science/hal-04882162 https://u-picardie.hal.science/hal-04882162v1/document https://u-picardie.hal.science/hal-04882162v1/file/ResSquare2025.pdf https://doi.org/10.21203/rs.3.rs-5549603/v1 |
| Rights: | http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.1FF8B974 |
| قاعدة البيانات: | BASE |
| DOI: | 10.21203/rs.3.rs-5549603/v1 |
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