ArticlePflugers Archiv : European journal of physiology2014
cAMP-PKA inhibition of SK3 channel reduced both Ca2+ entry and cancer cell migration by regulation of SK3-Orai1 complex.
Article in Pflugers Archiv : European journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- SPOP-mediated K27-linked non-degradative ubiquitination of KCNN3 suppressing HCC progression via the CTCF-SATB1 axis.Cell death & disease · 2026Article
- Reduced SK channel control of mesolimbic dopamine neuron firing drives reward seeking adaptations in chronic pain.bioRxiv : the preprint server for biology · 2025Article
- The multifaceted role of phosphodiesterase 4 in tumor: from tumorigenesis to immunotherapy.Frontiers in immunology · 2025Review
- CRAC and SK Channels: Their Molecular Mechanisms Associated with Cancer Cell Development.Cancers · 2022Review
- The Role of Lipids in CRAC Channel Function.Biomolecules · 2022Review
- Orai1 Boosts SK3 Channel Activation.Cancers · 2021Article
- Deciphering Molecular Mechanisms and Intervening in Physiological and Pathophysiological Processes of CaCells · 2021Review
- Furin Prodomain ppFurin Enhances CaCancers · 2021Article
- More Than Just Simple Interaction between STIM and Orai Proteins: CRAC Channel Function Enabled by a Network of Interactions with Regulatory Proteins.International journal of molecular sciences · 2021Review
- Molecular Choreography and Structure of CaMembranes · 2020Review
- PKA phosphorylation underlies functional recruitment of sarcolemmal SK2 channels in ventricular myocytes from hypertrophic hearts.The Journal of physiology · 2020Article
- Roles of endogenous ether lipids and associated PUFAs in the regulation of ion channels and their relevance for disease.Journal of lipid research · 2020Review
- Store-Operated CaInternational journal of molecular sciences · 2018Review
- The store-operated calcium channels in cancer metastasis: from cell migration, invasion to metastatic colonization.Frontiers in bioscience (Landmark edition) · 2018Article
- Intrinsic Disorder in Proteins with Pathogenic Repeat Expansions.Molecules (Basel, Switzerland) · 2017Review
- The SigmaR1 chaperone drives breast and colorectal cancer cell migration by tuning SK3-dependent CaOncogene · 2017Article
- Zinc transporters and dysregulated channels in cancers.Frontiers in bioscience (Landmark edition) · 2017Review
- Intracellular calcium oscillations in strongly metastatic human breast and prostate cancer cells: control by voltage-gated sodium channel activity.European biophysics journal : EBJ · 2016Article
- The role of extracellular calcium in bone metastasis.Journal of bone oncology · 2016Article
- Orai1 forms a signal complex with BKCa channel in mesenteric artery smooth muscle cells.Physiological reports · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SK3 channel mediates the migration of various cancer cells. When expressed in breast cancer cells, SK3 channel forms a complex with Orai1, a voltage-independent Ca(2+) channel. This SK3-Orai1 complex associates within lipid rafts where it controls a constitutive Ca(2+) entry leading to cancer cell migration and bone metastases development. Since cAMP was found to modulate breast cancer cell migration, we hypothesized that this could be explained by a modulation of SK3 channel activity. Herein, we study the regulation of SK3 channel by the cAMP-PKA pathway and the consequences for SK3-dependent Ca(2+) entry and cancer cell migration. We established that the beta-adrenergic receptor agonist, isoprenaline, or the direct adenylyl cyclase activator forskolin alone or in combination with the PDE4 inhibitor, CI-1044, decreased SK3 channel activity without modifying the expression of SK3 protein at the plasma membrane. Forskolin and CI-1044 reduced the SK3-dependent constitutive Ca(2+) entry and the SK3-dependent migration of MDA-MB-435s cells. PKA inhibition with KT 5720 reduced: (1) the effect of forskolin and CI-1044 by 50 % on Ca(2+) entry and (2) SK3 activity by inhibiting the serine phosphorylation of SK3. These cAMP-elevating agents displaced Orai1 protein outside lipid rafts in contrast to SK3, which remained in the lipid rafts fractions. All together, these results show that activation of the cAMP-PKA pathway decreases SK3 channel and SK3-Orai1 complex activities, leading to a decrease in both Ca(2+) entry and cancer cell migration. This work supports the potential use of cAMP-elevating agents to reduce cancer cell migration and may provide novel opportunities to address/prevent bone metastasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.