Reference - Detail
| RRC ID | 83346 |
|---|---|
| Author | Tóth S, Kaszás D, Sónyák J, Tőkés AM, Padányi R, Papp B, Nagy R, Vörös K, Csizmadia T, Tordai A, Enyedi Á. |
| Title | The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation. |
| Journal | 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. |
| Volume | 8(1) |
| Pages | 421 |
| Published | 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 |
| Resource | |
| Drosophila | 2165R-3 DGRC#115256 |