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Plasma Membrane Ca2+ ATPase Isoform 4 (PMCA4) Has an Important Role in Numerous Hallmarks of Pancreatic Cancer

1
Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK
2
Department of Biology, University of York, Heslington, York YO10 5DD, UK
3
Department of Pharmaceutical Science, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 218; https://doi.org/10.3390/cancers12010218
Received: 13 November 2019 / Revised: 8 January 2020 / Accepted: 10 January 2020 / Published: 16 January 2020
(This article belongs to the Special Issue Targeting Calcium Signaling in Cancer Cells)
Pancreatic ductal adenocarcinoma (PDAC) is largely resistant to standard treatments leading to poor patient survival. The expression of plasma membrane calcium ATPase-4 (PMCA4) is reported to modulate key cancer hallmarks including cell migration, growth, and apoptotic resistance. Data-mining revealed that PMCA4 was over-expressed in pancreatic ductal adenocarcinoma (PDAC) tumors which correlated with poor patient survival. Western blot and RT-qPCR revealed that MIA PaCa-2 cells almost exclusively express PMCA4 making these a suitable cellular model of PDAC with poor patient survival. Knockdown of PMCA4 in MIA PaCa-2 cells (using siRNA) reduced cytosolic Ca2+ ([Ca2+]i) clearance, cell migration, and sensitized cells to apoptosis, without affecting cell growth. Knocking down PMCA4 had minimal effects on numerous metabolic parameters (as assessed using the Seahorse XF analyzer). In summary, this study provides the first evidence that PMCA4 is over-expressed in PDAC and plays a role in cell migration and apoptotic resistance in MIA PaCa-2 cells. This suggests that PMCA4 may offer an attractive novel therapeutic target in PDAC. View Full-Text
Keywords: pancreatic ductal adenocarcinoma; plasma membrane Ca2+ ATPases 4 (PMCA4); cell migration; apoptosis; cancer metabolism pancreatic ductal adenocarcinoma; plasma membrane Ca2+ ATPases 4 (PMCA4); cell migration; apoptosis; cancer metabolism
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Sritangos, P.; Pena Alarcon, E.; James, A.D.; Sultan, A.; Richardson, D.A.; Bruce, J.I.E. Plasma Membrane Ca2+ ATPase Isoform 4 (PMCA4) Has an Important Role in Numerous Hallmarks of Pancreatic Cancer. Cancers 2020, 12, 218.

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