TRP channels and STIM/ORAI proteins: sensors and effectors of cancer and stroma cell migration.
Cancer cells are strongly influenced by host cells within the tumour stroma and vice versa. This leads to the development of a tumour microenvironment with distinct physical and chemical properties that are permissive for tumour progression. The ability to migrate plays a central role in this mutual interaction. Migration of cancer cells is considered as a prerequisite for tumour metastasis and the migration of host stromal cells is required for reaching the tumour site. Increasing evidence suggests that transient receptor potential (TRP) channels and STIM/ORAI proteins affect key calcium-dependent mechanisms implicated in both cancer and stroma cell migration. These include, among others, cytoskeletal remodelling, growth factor/cytokine signalling and production, and adaptation to tumour microenvironmental properties such as hypoxia and oxidative stress. In this review, we will summarize the current knowledge regarding TRP channels and STIM/ORAI proteins in cancer and stroma cell migration. We focus on how TRP channel or STIM/ORAI-mediated Ca(2+) signalling directly or indirectly influences cancer and stroma cell migration by affecting the above listed mechanisms.


BACKGROUND
This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24.
Institute of Physiology II, University of Münster, Münster, Germany.
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Nielsen
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Lindemann
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Schwab
D000222:Adaptation, Physiological; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D000071740:ORAI1 Protein; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism* / Q000502:physiology; D000071737:Stromal Interaction Molecule 1; D050051:Transient Receptor Potential Channels / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000502:physiology*
D015220:Calcium Channels; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D050051:Transient Receptor Potential Channels; D002118:Calcium