Chemotaxis of MDCK-F cells toward fibroblast growth factor-2 depends on transient receptor potential canonical channel 1.
ABSTRACT Movement toward the source of a chemoattractant gradient is a basic cellular property in health and disease. Enhanced migration during metastasis involves deregulated growth factor signaling. Growth factor stimulation and cell migration converge both on the important second messenger Ca(2+). To date, the molecular identification of Ca(2+) entry pathways activated by growth factors during chemotaxis is still an open issue. We investigated the involvement of the nonselective Ca(2+) channel TRPC1 (transient receptor potential canonical 1) in FGF-2 guided chemotaxis by means of time-lapse video microscopy and by functional Ca(2+) measurements. To specifically address TRPC1 function in transformed MDCK cells we altered the expression levels by siRNA or overexpression. We report that TRPC1 channels are required for the orientation of transformed MDCK cells in FGF-2 gradients because TRPC1 knockdown or pharmacological blockade prevented chemotaxis. Stimulation with FGF-2 triggered an immediate Ca(2+) influx via TRPC1 channels that depended on phospholipase C and phosphatidylinositol 3-kinase signaling. Impeding this Ca(2+) influx abolished chemotaxis toward FGF-2. This functional connection correlated with clustering of FGF receptors and TRPC1 channels as was observed by immunolabeling. These findings show the important interplay between growth factor signaling and Ca(2+) influx in chemotaxis.
- SourceAvailable from: Aurelie Chantome[Show abstract] [Hide abstract]
ABSTRACT: This review describes lipid raft ion channel complexes and EGFR in cancer cells•Complexes are composed of Ca2 + -activated K + (KCa), Cl- (ClCa) and Ca2 + channels•The modification of these lipid raft complexes by lipids is presented•This could lead to a novel therapeutic approach in tumor developmentBiochimica et Biophysica Acta (BBA) - Biomembranes. 11/2014;
- [Show abstract] [Hide abstract]
ABSTRACT: Cell migration is a central component of the metastatic cascade requiring a concerted action of ion channels and transporters (migration-associated transportome), cytoskeletal elements and signalling cascades. Ion transport proteins and aquaporins contribute to tumour cell migration and invasion among other things by inducing local volume changes and/or by modulating Ca(2+) and H(+) signalling. Targeting cell migration therapeutically bears great clinical potential, because it is a prerequisite for metastasis. Ion transport proteins appear to be attractive candidate target proteins for this purpose because they are easily accessible as membrane proteins and often overexpressed or activated in cancer. Importantly, a number of clinically widely used drugs are available whose anticipated efficacy as anti-tumour drugs, however, has now only begun to be evaluated.Philosophical Transactions of The Royal Society B Biological Sciences 01/2014; 369(1638):20130102. · 6.23 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Cancer cells are strongly influenced by host cells within the tumor stroma and vice versa. This leads to the development of a tumor microenvironment with distinct physical and chemical properties that are permissive for tumor progression. The ability to migrate plays a central role in this mutual interaction. Migration of cancer cells is considered as a prerequisite for tumor metastasis and the migration of host stromal cells is required for reaching the tumor 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 remodeling, growth factor/cytokine signaling and production, and adaptation to tumor 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 Ca2+ signaling directly or indirectly impact cancer and stroma cell migration by affecting the above listed mechanisms.British Journal of Pharmacology 04/2014; · 5.07 Impact Factor