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STIM1- and Orai1-mediated Ca(2+) oscillation orchestrates invadopodium formation and melanoma invasion.
- Source :
-
The Journal of cell biology [J Cell Biol] 2014 Nov 24; Vol. 207 (4), pp. 535-48. Date of Electronic Publication: 2014 Nov 17. - Publication Year :
- 2014
-
Abstract
- Ca(2+) signaling has been increasingly implicated in cancer invasion and metastasis, and yet, the underlying mechanisms remained largely unknown. In this paper, we report that STIM1- and Orai1-mediated Ca(2+) oscillations promote melanoma invasion by orchestrating invadopodium assembly and extracellular matrix (ECM) degradation. Ca(2+) oscillation signals facilitate invadopodial precursor assembly by activating Src. Disruption of Ca(2+) oscillations inhibited invadopodium assembly. Furthermore, STIM1 and Orai1 regulate the proteolysis activity of individual invadopodia. Mechanistically, Orai1 blockade inhibited the recycling of MT1-matrix metalloproteinase (MMP) to the plasma membrane and entrapped MT1-MMP in the endocytic compartment to inhibit ECM degradation. STIM1 knockdown significantly inhibited melanoma lung metastasis in a xenograft mouse model, implicating the importance of this pathway in metastatic dissemination. Our findings provide a novel mechanism for Ca(2+)-mediated cancer cell invasion and shed new light on the spatiotemporal organization of store-operated Ca(2+) signals during melanoma invasion and metastasis.<br /> (© 2014 Sun et al.)
- Subjects :
- Animals
Boron Compounds pharmacology
Calcium metabolism
Calcium Channels genetics
Cell Line, Tumor
Enzyme Activation
Extracellular Matrix metabolism
Humans
Imidazoles pharmacology
Lung Neoplasms drug therapy
Lung Neoplasms secondary
MCF-7 Cells
Matrix Metalloproteinase 14 metabolism
Matrix Metalloproteinase Inhibitors pharmacology
Melanoma metabolism
Membrane Proteins genetics
Mice
Mice, Nude
Neoplasm Invasiveness
Neoplasm Proteins genetics
Neoplasm Transplantation
ORAI1 Protein
Stromal Interaction Molecule 1
src-Family Kinases metabolism
Calcium Channels metabolism
Calcium Signaling
Lung Neoplasms prevention & control
Melanoma pathology
Membrane Proteins metabolism
Neoplasm Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1540-8140
- Volume :
- 207
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 25404747
- Full Text :
- https://doi.org/10.1083/jcb.201407082