The Calcium Pump PMCA4b Promotes Epithelial Cell Polarization and Lumen Formation

Overview

Journal Commun Biol

Specialty Biology

Date 2025 Mar 13

PMID 40075218

Authors

Sarolta Toth

Diana Kaszas

Janos Sonyak

Anna-Maria Tokes

Rita Padanyi

Bela Papp

Reka Nagy

Kinga Voros

Tamas Csizmadia

Attila Tordai

Agnes Enyedi

Affiliations

Soon will be listed here.

Abstract

Loss of epithelial cell polarity and tissue disorganization are hallmarks of carcinogenesis, in which Ca signaling plays a significant role. Here we demonstrate that the plasma membrane Ca pump PMCA4 (ATP2B4) is downregulated in luminal breast cancer, and this is associated with shorter relapse-free survival in patients with luminal A and B1 subtype tumors. Using the MCF-7 breast cancer cell model we show that PMCA4 silencing results in the loss of cell polarity while a forced increase in PMCA4b expression induces cell polarization and promotes lumen formation. We identify Arf6 as a regulator of PMCA4b endocytic recycling essential for PMCA4-mediated lumen formation. Silencing of the single pmca gene in Drosophila melanogaster larval salivary gland destroys lumen morphology suggesting a conserved role of PMCAs in lumen morphogenesis. Our findings point to a role of PMCA4 in controlling epithelial cell polarity, and in the maintenance of normal glandular tissue architecture.

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