Abstract
Epithelial-to-Mesenchymal transition (EMT) together with Mesenchymal-to-Epithelial transition (MET) are two celular transformations thought to participate in the process of cancer migration and metastasis acquisition. Multiple signals from the microenvironment have been reported to drive EMT. However, microenvironment signals that control EMT are still unknown. Here, we identified a hypothetical control mechanism of EMT by cell contact dependent activation of RPTPs. This mechanism was supported by simulation of relevant physiological scenarios, where six key EMT promoting microenvironment signals were taken into account. These simulations showed that RPTPs have the potential to prevent EMT and also to promote MET in several physiological scenarios, except when combined with hypoxia scenario. In these cases, 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.
Footnotes
Add new information suggested by readers 1) Inclusion of figure with the network model 2) Inclusion of the table with perturbations 3) Improve figure with the proposed mechanism. 4) Include a small description in intro with amoeboid and hybrid phenotypes.