Exploring the role of the Rab network in epithelial-to-mesenchymal transition.

Abstract

Motivation: Rab GTPases (Rabs) are crucial for membrane trafficking within mammalian cells, and their dysfunction is implicated in many diseases. This gene family plays a role in several crucial cellular processes. Network analyses can uncover the complete repertoire of interaction patterns across the Rab network, informing disease research, opening new opportunities for therapeutic interventions.

Results: We examined Rabs and their interactors in the context of epithelial-to-mesenchymal transition (EMT), an indicator of cancer metastasizing to distant organs. A Rab network was first established from analysis of literature and was gradually expanded. Our Python module, resnet, assessed its network resilience and selected an optimally sized, resilient Rab network for further analyses. Pathway enrichment confirmed its role in EMT. We then identified 73 candidate genes showing a strong up-/down-regulation, across 10 cancer types, in patients with metastasized tumours compared to only primary-site tumours. We suggest that their encoded proteins might play a critical role in EMT, and further in vitro studies are needed to confirm their role as predictive markers of cancer metastasis. The use of resnet within the systematic analysis approach described here can be easily applied to assess other gene families and their role in biological events of interest.

Availability and implementation: Source code for resnet is freely available at https://github.com/Unmani199/resnet.