Table 2.
Effect of calcium-related protein knockdown. A list of calcium-related proteins used in studies to test in parallel the effects of knockdown on both cellular function and calcium signaling is shown. The rationale is based on the overexpression of calcium channels, GPCR, calcium pumps, and calcium effectors and enzymes seen in patient tissue and aims to link cellular functional outcomes with changes in calcium signaling
| Protein knockdown | Functional outcome | Associated calcium signaling alteration | Reference | |
|---|---|---|---|---|
| Calcium Channels |
ORAI3 ORAI3 ORAI1 |
Inhibited in vitro proliferation and viability in MCF-7 Inhibited in vivo tumor growth in MCF-7 Reduced in vitro proliferation and viability in MCF-7 and MDA-MB-231 |
Reduced SOCE – Reduced SOCE |
Faouzi et al. 2011 Motiani et al. 2013 McAndrew et al. 2011 |
| ORAI1 or STIM1 | Reduced in vitro migration and invasion, and in vivo metastasis in MDA-MB-231 | Reduced SOCE | Yang et al. 2009 | |
| STIM1 | Inhibited in vivo tumor growth and metastasis in MDA-MB-231 | – | Miao et al. 2019 | |
| IP3R3 | Inhibited in vitro migration in MDA-MB-231 | Switched from ATP-stimulated global intracellular calcium signal to an oscillating one | Mound et al. 2017 | |
| IP3R2/3 | Reduced in vitro viability in MCF-7 | – | Singh et al. 2017a | |
| TRPM7 |
Reduced in vitro migration and in vivo metastasis in MDA-MB-231 Reduced in vitro viability in MCF-7 |
– Reduced resting calcium concentrations |
Middelbeek et al. 2012 Guilbert et al. 2009 |
|
| TRPM8 | Reduced in vitro migration in MDA-MB-231 | – | Liu et al. 2014 | |
| TRPV6 |
Reduced in vitro viability in T47D Reduced in vitro migration and invasion in MDA-MB-231 Reduced in vitro viability in T47D |
– – Reduced TRPV6 calcium flux |
Bolanz et al. 2008 Dhennin-Duthille et al. 2011 Peters et al. 2012 |
|
| MCU |
Reduced in vivo tumor growth and metastasis in MDA-MB-231 Reduced in vitro migration in MDA-MB-231 |
Reduced ATP-stimulated mitochondrial calcium uptake Reduced SOCE |
Tosatto et al. 2016 Tang et al. 2015 |
|
| VGCC |
Reduced in vitro invasion in MDA-MB-231 Reduced in vitro proliferation in MCF-7 |
– – |
Jacquemet et al. 2016 Taylor et al. 2008 |
|
| Calcium pumps | PMCA2 | Reduced in vitro proliferation in MDA-MB-231 | – | Peters et al. 2016 |
| SPCA2 | Reduced in vitro proliferation and colony formation in MCF-7 | Reduced resting calcium concentrations | Feng et al. 2010 | |
| GPCRs | P2Y2 |
Reduced in vivo primary tumor growth and metastasis in MDA-MB-231 Reduced in vivo primary tumor growth and metastasis, and in vitro migration and invasion in MDA-MB-231 |
– Reduced ATP-stimulated cytosolic calcium signaling |
Zhang et al. 2017 Jin et al. 2014 |
| Calcium effectors and enzymes | PKCζ | Reduced in vitro migration and invasion and in vivo metastasis in MDA-MB-231 | – | Paul et al. 2015, Smalley et al. 2019 |
| NFAT |
Reduced in vitro invasion in MDA-MB-231 Reduced in vitro migration and invasion, and in vivo tumor growth in 4T1 |
– – |
Kim et al. 2018 Quang et al. 2015 |
|
| – | – | MCF-7 vs MCF10A | Increased resting calcium concentrations | Jonathan Pottle et al. 2013 |
| – | – |
HBL100 vs SKBR3 MCF10A vs MDA-MB-231 |
Reduced capacity to release calcium from intracellular stores but a more robust calcium entry during SOCE |
Baldi et al. 2003 Motiani et al. 2010 |