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The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation
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The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation
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Paper
The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation
2024
Overview
Loss of epithelial cell polarity is a hallmark of carcinogenesis, in which Ca2+ signaling plays a role. Here we demonstrate that the plasma membrane Ca2+ pump PMCA4 is downregulated in luminal breast cancer, and this is associated with shorter relapse-free survival of patients with luminal A and B1 sub-type tumors. We find that in vitro silencing of PMCA4 in MCF-7 breast cancer cells induces internalization of E-cadherin and Dlg1 leading to a severe loss of cell polarity while re-expression of the b variant of PMCA4 restores cell polarity and promotes lumen formation mediated by the Arf6-trafficking pathway. We also demonstrate via an in vivo model using Drosophila melanogaster that silencing of the single pmca gene destroys lumen morphology in the larval salivary gland suggesting a conserved role of PMCAs in lumen morphogenesis. Additionally, enhanced secretory vesicle accumulation in PMCA(4)-deficient cells indicates a profound secretion defect both in vitro and in vivo. Our findings point to a novel role of PMCA4 in restoring epithelial cell polarity, and maintaining normal glandular tissue architecture.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
