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<p>Loss of epithelial cell polarity and tissue disorganization are hallmarks of carcinogenesis, in which Ca<sup>2+</sup> signaling plays a significant role. Here we demonstrate that the plasma membrane Ca<sup>2+</sup> 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 <i>pmca</i> gene in <i>Drosophila melanogaster</i> 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.</p>

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The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月12日

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  • Sarolta Tóth,
  • Diána Kaszás,
  • János Sónyák,
  • Anna-Mária Tőkés,
  • Rita Padányi,
  • Béla Papp,
  • Réka Nagy,
  • Kinga Vörös,
  • Tamás Csizmadia,
  • Attila Tordai,
  • Ágnes Enyedi

摘要

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.