PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position

• DOI: 10.1242/jcs.190215
• Publication Date: 2016-09-22T02:09:35Z
• Authors: Pablo Luján; Giulia Varsano; Teresa Rubio; Marco L. Hennrich; Timo Sachsenheimer; Manuel Gálvez-San...; Fernando Martín-B...; Anne-Claude Gavin; Britta Brügger; Maja Köhn
• Keywords: cell division; 0301 basic medicine; Epithelial Cells/cytology/metabolism; MCF-7 cell line; protein tyrosine phosphatase; Madin Darby Canine Kidney Cells; Protein Tyrosine Phosphatases/metabolism; Models; cell growth assay; phosphatase of regenerating liver 3; animal; apical membrane; PTP4A3; cancer cell; Cancer; Cell Polarity; MDCK cell line; cell invasion; unclassified drug; Neoplasm Proteins; 3. Good health; cell polarity; priority journal; dog; Cell polarity; MCF-7 Cells; cell disruption; Epithelia; PRL-3; cancer cell line; PTP4A3 protein; Research Article; 572; CACO 2 cell line; mitosis spindle; Mitosis; cytokinesis; Models, Biological; Article; cell shape; Midbody; 03 medical and health sciences; breast cancer; Dogs; tumor protein; Caco-2 cell line; Neoplasm Proteins/metabolism; Animals; Humans; controlled study; human; Cell Shape; Cytokinesis; mitosis; Epithelial Cells; biological model; Biological; abscission; cytology; Caco-2 Cells; Protein Tyrosine Phosphatases; epithelium cell; metabolism; cell structure

ABSTRACT 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 invasion and the formation of multiple ectopic, fully polarized lumens in cysts. Both processes disrupt epithelial architecture and are hallmarks of cancer. The pathological relevance of these findings is supported by the knockdown of endogenous PRL-3 in MCF-7 breast cancer cells grown in three-dimensional branched structures, showing the rescue from multiple-lumen- to single-lumen-containing branch ends. Mechanistically, it has been previously shown that ectopic lumens can arise from midbodies that have been mislocalized through the loss of mitotic spindle orientation or through 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, instead, PRL-3 accelerates cytokinesis, suggesting that this process is an alternative new mechanism for ectopic lumen formation in MDCK cysts. The disruption of epithelial architecture by PRL-3 revealed here is a newly recognized mechanism for PRL-3-promoted cancer progression.