The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation.

ABSTRACT: Loss of epithelial cell polarity and tissue disorganization are hallmarks of carcinogenesis, in which Ca²⁺ signaling plays a significant role. Here we demonstrate that the plasma membrane Ca²⁺ 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

SUBMITTER: Toth S 

PROVIDER: S-EPMC11904214 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature