Subcellular distribution of S100 proteins in tumor cells and their relocation in response to calcium activation.
S100 proteins, a subgroup of the EF-hand Ca2+-binding protein family, regulate a variety of cellular processes via interaction with different target proteins. Several pathological disorders, including cancer, are linked to altered Ca2+ homeostasis and might involve the multifunctional S100 proteins, which are expressed in a cell- and tissue-specific manner. The present work demonstrates a distinct intracellular localization of S100A6, S100A4, and S100A2 in two tumor cell lines derived from metastatic epithelial breast adenocarcinoma (MDA-MB231) and cervical carcinoma (HeLa). Treatment of the cells by thapsigargin, the ionophore A23187, or cyclic ADP-ribose, to increase [Ca2+]i via different pathways, led to relocation of S100A6 and S100A4 but only partially of the nuclear S100A2, as demonstrated by confocal laser scanning microscopy. These findings support the hypothesis that S100 proteins could play a crucial role in the regulation of Ca2+ homeostasis in cancer cells.
Mueller
A
A
Department of Pediatrics, University of Zurich, Switzerland.
Bächi
T
T
Höchli
M
M
Schäfer
B W
BW
Heizmann
C W
CW
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000032:analysis*; D018797:Cell Cycle Proteins; D002630:Chemotactic Factors / Q000032:analysis*; D036563:Cyclic ADP-Ribose; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D000075383:S100 Calcium Binding Protein A6; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000032:analysis*; D013347:Subcellular Fractions; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; D000075383:S100 Calcium Binding Protein A6; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C098997:S100A2 protein, human; C055351:S100A6 protein, human; D036563:Cyclic ADP-Ribose; C077591:S100A4 protein, human; D000246:Adenosine Diphosphate Ribose; D019284:Thapsigargin; D002118:Calcium