The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation

Toth, S.; Kaszas, D.; Sonyak, J.; Tokes, A.-M.; Padanyi, R.; Papp, B.; Nagy, R.; Vörös, K.; Csizmadia, T.; Tordai, A.; Enyedi, A.

doi:10.1101/2024.01.20.576436

bioRxiv · 10.1101/2024.01.20.576436

The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation

Toth, S.·Kaszas, D.·Sonyak, J.·Tokes, A.-M.·Padanyi, R.·Papp, B.·Nagy, R.·Vörös, K.·Csizmadia, T.·Tordai, A.·Enyedi, A.

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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 in 2D and 3D cell cultures. We identify Arf6 as a novel regulator of PMCA4b endocytic recycling essential for PMCA4 regulated 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 novel role of PMCA4 in controlling epithelial cell polarity, and in the maintenance of normal glandular tissue architecture.

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Toth, S., Kaszas, D., Sonyak, J., Tokes, A.-M., Padanyi, R., Papp, B., Nagy, R., Vörös, K., Csizmadia, T., Tordai, A., Enyedi, A.. 2024-01-21. The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation. https://doi.org/10.1101/2024.01.20.576436

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