Τίτλος:
Differential effects of calcium on PI3K-Akt and HIF-1α survival pathways
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Calcium signaling participates in the regulation of numberless cellular functions including cell cycle progression and cellular migration, important processes for cancer expansion. Cancer cell growth, migration, and invasion are typically supported by PI3K/Akt activation, while a hypoxic environment is critical in cancer development. Accordingly, in the present study, we aimed at investigating whether perturbations in calcium homeostasis induce alterations of HIF-1α and activate Akt levels in epithelial A549 and A431 cells. Survival was drastically reduced in the presence of calcium chelator BAPTA-AM and thapsigargin, a SERCA inhibitor inducing store-operated calcium entry, to a lesser extent. Calcium chelation provoked a transient but strong upregulation of HIF-1α protein levels and accumulation in the nucleus, whereas in the presence of thapsigargin, HIF-1α levels were rapidly abolished before reaching and exceeding control levels. Despite cell death, calcium chelation merely inhibited Akt, which was significantly activated in the presence of thapsigargin. Moreover, when store-operated calcium entry was simulated by reintroducing calcium ions in cell suspensions, Akt was rapidly activated in the absence of any growth factor. These data further underscore the growing importance of calcium entry and directly link this elementary event of calcium homeostasis to the Akt pathway, which is commonly deregulated in cancer. © 2016, Springer Science+Business Media Dordrecht.
Συγγραφείς:
Divolis, G.
Mavroeidi, P.
Mavrofrydi, O.
Papazafiri, P.
Περιοδικό:
Cell Biology and Toxicology
Εκδότης:
SPRINGER NETHERLANDS
Λέξεις-κλειδιά:
calcium; calcium chelating agent; ethylene glycol 1,2 bis(2 aminophenyl) ether n,n,n',n' tetraacetic acid; growth factor; hypoxia inducible factor 1alpha; phosphatidylinositol 3 kinase; protein kinase B; thapsigargin; 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; calcium; chelating agent; egtazic acid; hypoxia inducible factor 1alpha; phosphatidylinositol 3 kinase; protein kinase B; signal peptide; thapsigargin, A431 cell line; A549 cell line; Article; calcium cell level; calcium homeostasis; calcium signaling; calcium transport; cell death; cell survival; cell suspension; cell viability; chelation; controlled study; cytotoxicity; enzyme activation; enzyme inhibition; epithelium cell; human; human cell; membrane channel; priority journal; squamous cell carcinoma cell line; upregulation; A-549 cell line; analogs and derivatives; calcium signaling; drug effects; enzymology; lung alveolus epithelium cell; metabolism; transcription initiation; tumor cell line, A549 Cells; Alveolar Epithelial Cells; Calcium; Calcium Signaling; Cell Line, Tumor; Chelating Agents; Egtazic Acid; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intercellular Signaling Peptides and Proteins; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Thapsigargin; Transcriptional Activation
DOI:
10.1007/s10565-016-9345-x
