| First Author | Feng M | Year | 2010 |
| Journal | Cell | Volume | 143 |
| Issue | 1 | Pages | 84-98 |
| PubMed ID | 20887894 | Mgi Jnum | J:167918 |
| Mgi Id | MGI:4881362 | Doi | 10.1016/j.cell.2010.08.040 |
| Citation | Feng M, et al. (2010) Store-independent activation of Orai1 by SPCA2 in mammary tumors. Cell 143(1):84-98 |
| abstractText | Ca(2+) is an essential and ubiquitous second messenger. Changes in cytosolic Ca(2+) trigger events critical for tumorigenesis, such as cellular motility, proliferation, and apoptosis. We show that an isoform of Secretory Pathway Ca(2+)-ATPase, SPCA2, is upregulated in breast cancer-derived cells and human breast tumors, and suppression of SPCA2 attenuates basal Ca(2+) levels and tumorigenicity. Contrary to its conventional role in Golgi Ca(2+) sequestration, expression of SPCA2 increased Ca(2+) influx by a mechanism dependent on the store-operated Ca(2+) channel Orai1. Unexpectedly, SPCA2-Orai1 signaling was independent of ER Ca(2+) stores or STIM1 and STIM2 sensors and uncoupled from Ca(2+)-ATPase activity of SPCA2. Binding of the SPCA2 amino terminus to Orai1 enabled access of its carboxyl terminus to Orai1 and activation of Ca(2+) influx. Our findings reveal a signaling pathway in which the Orai1-SPCA2 complex elicits constitutive store-independent Ca(2+) signaling that promotes tumorigenesis. |
