Disruption of epithelial architecture is a fundamental event during epithelial tumorigenesis. We show that the expression of the cancer-promoting phosphatase PRL-3 (PTP4A3), which is overexpressed in several epithelial cancers, in polarized epithelial MDCK and Caco2 cells leads to invasive and also multiple ectopic fully polarized lumen-containing cysts. Both processes disrupt epithelial architecture and are hallmarks of cancer. The pathological relevance of these findings is supported by the knock-down of endogenous PRL-3 in MCF-7 breast cancer cells grown in 3-dimensional branched structures, showing the rescue from multiple-lumen to single lumen containing branch ends. Mechanistically, it was previously shown that ectopic lumens could arise from midbodies that were mislocalized by the loss of mitotic spindle orientation or by the loss of asymmetric abscission. Here, we show that PRL-3 triggers ectopic lumen formation through midbody mispositioning without altering the spindle orientation or asymmetric abscission, but accelerating cytokinesis suggesting this process as an alternative new mechanism for ectopic lumen formation in MDCK cysts. The here discovered disruption of epithelial architecture by PRL-3 is a newly recognized mechanism for PRL-3-promoted cancer progression.
- Received March 31, 2016.
- Accepted September 16, 2016.
- © 2016. Published by The Company of Biologists Ltd
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