Store-Independent Activation of Orai1 by SPCA2 in Mammary Tumors

Mingye Feng; Desma M Grice; Helen Faddy; Nguyen Nguyen; Sharon Leitch; Yingyu Wang; Sabina Muend; Paraic A Kenny; Saraswati Sukumar; Sarah J Roberts-Thomson; Gregory R Monteith; Rajini Rao

doi:10.1016/j.cell.2010.08.040

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Store-Independent Activation of Orai1 by SPCA2 in Mammary Tumors

Journal article

Peer reviewed

Store-Independent Activation of Orai1 by SPCA2 in Mammary Tumors

Mingye Feng, Desma M Grice, Helen Faddy, Nguyen Nguyen, Sharon Leitch, Yingyu Wang, Sabina Muend, Paraic A Kenny, Saraswati Sukumar, Sarah J Roberts-Thomson, …

Cell, Vol.143(1), pp.84-98

2010

DOI: https://doi.org/10.1016/j.cell.2010.08.040

PMCID: PMC2950964

PMID: 20887894

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Abstract

cellbio

humdisease

signaling

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.

Details

Title: Store-Independent Activation of Orai1 by SPCA2 in Mammary Tumors
Authors: Mingye Feng (Author) - Johns Hopkins University
Desma M Grice (Author) - University of Queensland
Helen Faddy (Author) - University of Queensland
Nguyen Nguyen (Author) - Johns Hopkins University
Sharon Leitch (Author) - Johns Hopkins University
Yingyu Wang (Author) - Johns Hopkins University
Sabina Muend (Author) - Johns Hopkins University
Paraic A Kenny (Author) - University of California, Berkeley
Saraswati Sukumar (Author) - Johns Hopkins University
Sarah J Roberts-Thomson (Author) - University of Queensland
Gregory R Monteith (Author) - University of Queensland
Rajini Rao (Author) - Johns Hopkins University
Publication details: Cell, Vol.143(1), pp.84-98
Publisher: Cell Press
DOI: 10.1016/j.cell.2010.08.040
ISSN: 1097-4172
PMID: 20887894; PMC2950964
Organisation Unit: School of Health and Behavioural Sciences - Legacy; School of Health and Sport Sciences - Legacy; University of the Sunshine Coast, Queensland; School of Health - Biomedicine
Language: English
Record Identifier: 99477806002621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology

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