RRC ID 83346
著者 Tóth S, Kaszás D, Sónyák J, Tőkés AM, Padányi R, Papp B, Nagy R, Vörös K, Csizmadia T, Tordai A, Enyedi Á.
タイトル The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation.
ジャーナル Commun Biol
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 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.
巻・号 8(1)
ページ 421
公開日 2025-3-12
DOI 10.1038/s42003-025-07814-5
PII 10.1038/s42003-025-07814-5
PMID 40075218
PMC PMC11904214
MeSH Animals Breast Neoplasms / genetics Breast Neoplasms / metabolism Breast Neoplasms / pathology Cell Polarity* / genetics Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila melanogaster* / genetics Epithelial Cells* / metabolism Female Humans Larva / genetics Larva / growth & development Larva / metabolism MCF-7 Cells Plasma Membrane Calcium-Transporting ATPases* / genetics Plasma Membrane Calcium-Transporting ATPases* / metabolism
IF 4.165
リソース情報
ショウジョウバエ 2165R-3 DGRC#115256