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      Emerging role of TRP channels in cell migration: from tumor vascularization to metastasis

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          Abstract

          Transient Receptor Potential (TRP) channels modulate intracellular Ca 2+ concentrations, controlling critical cytosolic and nuclear events that are involved in the initiation and progression of cancer. It is not, therefore, surprising that the expression of some TRP channels is altered during tumor growth and metastasis. Cell migration of both epithelial and endothelial cells is an essential step of the so-called metastatic cascade that leads to the spread of the disease within the body. It is in fact required for both tumor vascularization as well as for tumor cell invasion into adjacent tissues and intravasation into blood/lymphatic vessels. Studies from the last 15 years have unequivocally shown that the ion channles and the transport proteins also play important roles in cell migration. On the other hand, recent literature underlies a critical role for TRP channels in the migration process both in cancer cells as well as in tumor vascularization. This will be the main focus of our review. We will provide an overview of recent advances in this field describing TRP channels contribution to the vascular and cancer cell migration process, and we will systematically discuss relevant molecular mechanism involved.

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          Most cited references109

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          Angiogenesis in life, disease and medicine.

          The growth of blood vessels (a process known as angiogenesis) is essential for organ growth and repair. An imbalance in this process contributes to numerous malignant, inflammatory, ischaemic, infectious and immune disorders. Recently, the first anti-angiogenic agents have been approved for the treatment of cancer and blindness. Angiogenesis research will probably change the face of medicine in the next decades, with more than 500 million people worldwide predicted to benefit from pro- or anti-angiogenesis treatments.
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            TRP channels.

            The TRP (Transient Receptor Potential) superfamily of cation channels is remarkable in that it displays greater diversity in activation mechanisms and selectivities than any other group of ion channels. The domain organizations of some TRP proteins are also unusual, as they consist of linked channel and enzyme domains. A unifying theme in this group is that TRP proteins play critical roles in sensory physiology, which include contributions to vision, taste, olfaction, hearing, touch, and thermo- and osmosensation. In addition, TRP channels enable individual cells to sense changes in their local environment. Many TRP channels are activated by a variety of different stimuli and function as signal integrators. The TRP superfamily is divided into seven subfamilies: the five group 1 TRPs (TRPC, TRPV, TRPM, TRPN, and TRPA) and two group 2 subfamilies (TRPP and TRPML). TRP channels are important for human health as mutations in at least four TRP channels underlie disease.
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              An introduction to TRP channels.

              The aim of this review is to provide a basic framework for understanding the function of mammalian transient receptor potential (TRP) channels, particularly as they have been elucidated in heterologous expression systems. Mammalian TRP channel proteins form six-transmembrane (6-TM) cation-permeable channels that may be grouped into six subfamilies on the basis of amino acid sequence homology (TRPC, TRPV, TRPM, TRPA, TRPP, and TRPML). Selected functional properties of TRP channels from each subfamily are summarized in this review. Although a single defining characteristic of TRP channel function has not yet emerged, TRP channels may be generally described as calcium-permeable cation channels with polymodal activation properties. By integrating multiple concomitant stimuli and coupling their activity to downstream cellular signal amplification via calcium permeation and membrane depolarization, TRP channels appear well adapted to function in cellular sensation. Our review of recent literature implicating TRP channels in neuronal growth cone steering suggests that TRPs may function more widely in cellular guidance and chemotaxis. The TRP channel gene family and its nomenclature, the encoded proteins and alternatively spliced variants, and the rapidly expanding pharmacology of TRP channels are summarized in online supplemental material.
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                Author and article information

                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                05 November 2013
                2013
                : 4
                : 311
                Affiliations
                [1] 1Department of Life Sciences and Systems Biology, Nanostructured Interfaces and Surfaces Centre of Excellence, University of Torino Torino, Italy
                [2] 2Inserm U1003, Equipe labellisée par la Ligue Nationale contre le cancer, Université des Sciences et Technologies de Lille Villeneuve d’Ascq, France
                Author notes

                Edited by: Andrea Becchetti, University of Milano-Bicocca, Italy

                Reviewed by: Giorgio Santoni, University of Camerino, Italy; Haliama Ouadid-Ahidouch, University of Picardie Jules Verne, France; Olivier Soriani, Centre National de la Recherche Scientifique, France

                *Correspondence: Alessandra Fiorio Pla, Department of Life Sciences and Systems Biology, Nanostructured Interfaces and Surfaces Centre of Excellence, University of Torino, Via Accademia Albertina, 13 10123 Torino, Italy e-mail: alessandra.fiorio@ 123456unito.it;
                Dimitra Gkika, Laboratoire de Physiologie Cellulaire, Université des Sciences et Technologies de Lille, Rue Paul Langevin, Bât.SN3 - 2éme étage - porte 221, 59655 Villeneuve d’Ascq, France e-mail: dimitra.gkika@ 123456univ-lille1.fr

                This article was submitted to Membrane Physiology and Membrane Biophysics, a section of the journal Frontiers in Physiology.

                Article
                10.3389/fphys.2013.00311
                3817680
                24204345
                18458941-8729-4ef4-8b0e-81dab71d450d
                Copyright © 2013 Fiorio Pla and Gkika.

                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.

                History
                : 04 July 2013
                : 11 October 2013
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 117, Pages: 12, Words: 10935
                Categories
                Physiology
                Review Article

                Anatomy & Physiology
                cancer cells,tumor angiogenesis,cell migration,trp channels,orai/stim1
                Anatomy & Physiology
                cancer cells, tumor angiogenesis, cell migration, trp channels, orai/stim1

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