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PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position
Disruption of epithelial architecture is a fundamental event during epithelial tumorigenesis. We show that the expression of the cancerpromoting 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 threedimensional branched structures, showing the rescue from multiplelumen- 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 throughmidbody 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. ; Deutsche Forschungsgemeinschaft within the Emmy-Noether program to M.K. [grant number KO 4013/1-1]. T.R. thanks European Molecular Biology Laboratory (EMBL) and Marie Curie Actions program (European Commission) for the EMBL Interdisciplinary Postdoc (EIPOD) fellowship. B.B. was supported by Deutsche Forschungsgemeinschaft [grant number TRR 83]. This work was also supported by grants from Ministerio de Economı́a y Competitividad (MINECO) [grant numbers BFU2015-71244-ERC; BFU2014-52125-REDT; BFU2014-57831 to F.M-B.]. ; Peer Reviewed
PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position
Disruption of epithelial architecture is a fundamental event during epithelial tumorigenesis. We show that the expression of the cancerpromoting 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 threedimensional branched structures, showing the rescue from multiplelumen- 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 throughmidbody 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. ; Deutsche Forschungsgemeinschaft within the Emmy-Noether program to M.K. [grant number KO 4013/1-1]. T.R. thanks European Molecular Biology Laboratory (EMBL) and Marie Curie Actions program (European Commission) for the EMBL Interdisciplinary Postdoc (EIPOD) fellowship. B.B. was supported by Deutsche Forschungsgemeinschaft [grant number TRR 83]. This work was also supported by grants from Ministerio de Economı́a y Competitividad (MINECO) [grant numbers BFU2015-71244-ERC; BFU2014-52125-REDT; BFU2014-57831 to F.M-B.]. ; Peer Reviewed
PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position
Luján, Pablo (author) / Varsano, Giulia (author) / Rubio, Teresa (author) / Hennrich, Marco L. (author) / Sachseheimer, Timo (author) / Gálvez-Santisteban, Manuel (author) / Martín-Belmonte, Fernando (author) / Gavin, Anne-Claude (author) / Brügger, Britta (author) / Köhn, Maja (author)
2016-09-16
Article (Journal)
Electronic Resource
English
DDC:
720
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