The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation
Abstrak
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.
Topik & Kata Kunci
Penulis (11)
Sarolta Tóth
Diána Kaszás
János Sónyák
Anna-Mária Tőkés
Rita Padányi
Béla Papp
Réka Nagy
Kinga Vörös
Tamás Csizmadia
Attila Tordai
Ágnes Enyedi
Akses Cepat
- Tahun Terbit
- 2025
- Sumber Database
- DOAJ
- DOI
- 10.1038/s42003-025-07814-5
- Akses
- Open Access ✓