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bioRxiv · 10.1101/609263

Network modelling of Epithelial-to-Mesenchymal transition reveals a putative role of RPTPs for the control of metastasis.

Pais, R. J.
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Abstract

Epithelial-to-Mesenchymal Transition (EMT) together with Mesenchymal-to-Epithelial Transition (MET) are two natural processes thought to participate in the process of metastasis. Multiple signals from the microenvironment have been reported to drive EMT. However, microenvironment signals that control EMT and promote MET are still unknown. Here, we analysed a regulatory network of EMT involving 8 microenvironment signals to evaluate the role of cell contact signals on the switching between Epithelial and Mesenchymal-like phenotypes. The results demonstrated that RPTP activation by cell contacts have the potential to control EMT and promote MET in the presence of 5 EMT driving signals under physiological scenarios. These simulations also showed that hypoxia inhibits the RPTPs capacity of controlling EMT. In this case, FAT4 activation by cell contacts functions as an alternative control mechanism of EMT except under chronic inflammation, providing a theoretical explanation for the observed correlation between hypoxia and metastasis under chronic inflammation. Taken together, we propose here a natural control mechanism of EMT that supports the idea that this process is tightly regulated by the microenvironment.\n\nHighlightsO_LICell contact dependent RPTP inhibit EMT and triggers MET in the presence of 5 EMT driving signals in silico.\nC_LIO_LIA proposed molecular mechanism for the control of EMT by cell contact dependent RPTPs.\nC_LIO_LIA proposed explanation for the observed MET in vitro and the correlation between hypoxia and metastasis in vivo.\nC_LI

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Pais, R. J.. 2019-04-15. Network modelling of Epithelial-to-Mesenchymal transition reveals a putative role of RPTPs for the control of metastasis.. https://doi.org/10.1101/609263

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