Oncotarget

Research Papers:

The orthologous Tbx transcription factors Omb and TBX2 induce epithelial cell migration and extrusion in vivo without involvement of matrix metalloproteinases

Jie Shen _, Juan Lu, Liyuan Sui, Dan Wang, Meizhen Yin, Inka Hoffmann, Anne Legler and Gert O. Pflugfelder

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Oncotarget. 2014; 5:11998-12015. https://doi.org/10.18632/oncotarget.2426

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Abstract

Jie Shen1, Juan Lu1, Liyuan Sui1, Dan Wang1, Meizhen Yin2, Inka Hoffmann3, Anne Legler3 and Gert O. Pflugfelder3

1 Department of Entomology, China Agricultural University, Beijing, China

2 Key Laboratory of Carbon Fiber and Functional Polymers, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, China

3 Institute of Genetics, Johannes Gutenberg-University, Mainz, Germany

Correspondence:

Jie Shen, email:

Gert O. Pflugfelder, email:

Keywords: TBX2; invasion; E-cadherin; extracellular matrix; Drosophila wing epithelium, optomotor-blind

Received: June 02, 2014 Accepted: September 02, 2014 Published: September 02, 2014

Abstract

The transcription factors TBX2 and TBX3 are overexpressed in various human cancers. Here, we investigated the effect of overexpressing the orthologous Tbx genes Drosophila optomotor-blind (omb) and human TBX2 in the epithelium of the Drosophila wing imaginal disc and observed two types of cell motility. Omb/TBX2 overexpressing cells could move within the plane of the epithelium. Invasive cells migrated long-distance as single cells retaining or regaining normal cell shape and apico-basal polarity in spite of attenuated apical DE-cadherin concentration. Inappropriate levels of DE-cadherin were sufficient to drive cell migration in the wing disc epithelium. Omb/TBX2 overexpression and reduced DE-cadherin-dependent adhesion caused the formation of actin-rich lateral cell protrusions. Omb/TBX2 overexpressing cells could also delaminate basally, penetrating the basal lamina, however, without degradation of extracellular matrix. Expression of Timp, an inhibitor of matrix metalloproteases, blocked neither intraepithelial motility nor basal extrusion. Our results reveal an MMP-independent mechanism of cell invasion and suggest a conserved role of Tbx2-related proteins in cell invasion and metastasis-related processes.


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