TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival
| Autor: | Pierre Gosset, Matthieu Vandenberghe, Alexandre Bokhobza, Leonardo Farsetti, Natalia Prevarskaya, Adriana Mihalache, Emmanuelle Germain, Philippe Clézardin, Christoph Romanin, Fabien Vanden Abeele, V’yacheslav Lehen’kyi, Roman Skryma, Maylis Raphaël, Sergiy Khalimonchyk, Benjamin Beck |
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| Přispěvatelé: | Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut Catholique de Lille (ICL), Université catholique de Lille (UCL), Université Lille Nord (France), Johannes Kepler Universität Linz (JKU), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty TRPV6 ORAI1 Protein Carcinogenesis Cell Survival [SDV]Life Sciences [q-bio] Mice Nude TRPV Cation Channels chemistry.chemical_element Apoptosis Bone Neoplasms Calcium Biology Endoplasmic Reticulum Transient receptor potential channel Cell Line Tumor Internal medicine medicine Animals Humans Neoplasm Invasiveness Annexin A1 Calcium metabolism Multidisciplinary Voltage-dependent calcium channel ORAI1 Calcium channel Cell Membrane S100 Proteins Prostatic Neoplasms Immunohistochemistry Xenograft Model Antitumor Assays Neoplasm Proteins Radiography Protein Transport HEK293 Cells Phenotype Endocrinology PNAS Plus chemistry Disease Progression Cancer research Calcium Channels Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2014, 111 (37) |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1413409111 |
| Popis: | International audience; Transient receptor potential vanilloid subfamily member 6 (TRPV6) is a highly selective calcium channel that has been considered as a part of store-operated calcium entry (SOCE). Despite its first discovery in the early 2000s, the role of this channel in prostate cancer (PCa) remained, until now, obscure. Here we show that TRPV6 mediates calcium entry, which is highly increased in PCa due to the remodeling mechanism involving the translocation of the TRPV6 channel to the plasma membrane via the Orai1/TRPC1-mediated Ca(2+)/Annexin I/S100A11 pathway, partially contributing to SOCE. The TRPV6 calcium channel is expressed de novo by the PCa cell to increase its survival by enhancing proliferation and conferring apoptosis resistance. Xenografts in nude mice and bone metastasis models confirmed the remarkable aggressiveness of TRPV6-overexpressing tumors. Immunohistochemical analysis of these demonstrated the increased expression of clinical markers such as Ki-67, prostate specific antigen, synaptophysin, CD31, and CD56, which are strongly associated with a poor prognosis. Thus, the TRPV6 channel acquires its oncogenic potential in PCa due to the remodeling mechanism via the Orai1-mediated Ca(2+)/Annexin I/S100A11 pathway. |
| Databáze: | OpenAIRE |
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