Store-independent activation of Orai1 by SPCA2 in mammary tumors

Feng, Mingye, Grice, Desma, Faddy, Helen, Nguyen, Nguyen, Leitch, Sharon, Wang, Yingyu, Muend, Sabina, Kenny, Paraic A, Sukumar, Saraswati, Roberts-Thomson, Sarah J., Monteith, Gregory R. and Rao, Rajini (2010) Store-independent activation of Orai1 by SPCA2 in mammary tumors. Cell, 143 1: 84-98. doi:10.1016/j.cell.2010.08.040

Author Feng, Mingye
Grice, Desma
Faddy, Helen
Nguyen, Nguyen
Leitch, Sharon
Wang, Yingyu
Muend, Sabina
Kenny, Paraic A
Sukumar, Saraswati
Roberts-Thomson, Sarah J.
Monteith, Gregory R.
Rao, Rajini
Title Store-independent activation of Orai1 by SPCA2 in mammary tumors
Journal name Cell   Check publisher's open access policy
ISSN 0092-8674
Publication date 2010-10-01
Sub-type Article (original research)
DOI 10.1016/j.cell.2010.08.040
Volume 143
Issue 1
Start page 84
End page 98
Total pages 15
Editor Emilie Marcus
Meredith Adinolfi
Place of publication Cambridge, MA, U.S.A.
Publisher Cell Press
Collection year 2011
Language eng
Subject 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
111601 Cell Physiology
920102 Cancer and Related Disorders
Formatted abstract
Ca2+ is an essential and ubiquitous second messenger. Changes in cytosolic Ca2+ trigger events critical for tumorigenesis, such as cellular motility, proliferation, and apoptosis. We show that an isoform of Secretory Pathway Ca2+-ATPase, SPCA2, is upregulated in breast cancer-derived cells and human breast tumors, and suppression of SPCA2 attenuates basal Ca2+ levels and tumorigenicity. Contrary to its conventional role in Golgi Ca2+ sequestration, expression of SPCA2 increased Ca2+ influx by a mechanism dependent on the store-operated Ca2+ channel Orai1. Unexpectedly, SPCA2-Orai1 signaling was independent of ER Ca2+ stores or STIM1 and STIM2 sensors and uncoupled from Ca2+-ATPase activity of SPCA2. Binding of the SPCA2 amino terminus to Orai1 enabled access of its carboxyl terminus to Orai1 and activation of Ca2+ influx. Our findings reveal a signaling pathway in which the Orai1-SPCA2 complex elicits constitutive store-independent Ca2+ signaling that promotes tumorigenesis.
© 2010 Elsevier Inc.
Keyword Cellbio
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Official 2011 Collection
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Created: Tue, 02 Nov 2010, 11:50:26 EST by Charna Kovacevic on behalf of School of Pharmacy