ORAI1 regulates sustained cytosolic free calcium fluctuations during breast cancer cell apoptosis and apoptotic resistance via a STIM1 independent pathway

© 2021 Federation of American Societies for Experimental Biology..

Excessive rapid increases in cytosolic free Ca2+ have a clear association with the induction of cancer cell death. Whereas, characterizing the Ca2+ signaling events that occur during the progression of the apoptotic cascade over a period of hours or days, has not yet been possible. Now using genetically encoded Ca2+ indicators complemented with automated epifluorescence microscopy we have shown that staurosporine-induced apoptosis in MDA-MB-231 breast cancer cells was associated with delayed development of cytosolic free Ca2+ fluctuations, which were then maintained for 24 h. These cytosolic free Ca2+ fluctuations were dependent on the Ca2+ channel ORAI1. Silencing of ORAI1, but not its canonical activators STIM1 and STIM2, promoted apoptosis in this model. The pathway for this regulation implicates a mechanism previously associated with the migration of cancer cells involving ORAI1, the chaperone protein SigmaR1, and Ca2+ -activated K+ channels.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:36

Enthalten in:

FASEB journal : official publication of the Federation of American Societies for Experimental Biology - 36(2022), 1 vom: 21. Jan., Seite e22108

Sprache:

Englisch

Beteiligte Personen:

Bassett, John J [VerfasserIn]
Robitaille, Mélanie [VerfasserIn]
Peters, Amelia A [VerfasserIn]
Bong, Alice H L [VerfasserIn]
Taing, Meng-Wong [VerfasserIn]
Wood, Ian A [VerfasserIn]
Sadras, Francisco [VerfasserIn]
Roberts-Thomson, Sarah J [VerfasserIn]
Monteith, Gregory R [VerfasserIn]

Links:

Volltext

Themen:

Breast cancer
Calcium
Calcium signaling
Cell death
GCaMP6
Journal Article
Neoplasm Proteins
ORAI1
ORAI1 Protein
ORAI1 protein, human
Research Support, Non-U.S. Gov't
STIM1 protein, human
SY7Q814VUP
Stromal Interaction Molecule 1

Anmerkungen:

Date Completed 11.01.2022

Date Revised 11.01.2022

published: Print

Citation Status MEDLINE

doi:

10.1096/fj.202002031RR

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM334756391