An integrated approach to infer cross-talks between intracellular protein transport and signaling pathways

Abstract

BackgroundThe endomembrane system, known as secretory pathway, is responsible for the synthesis and transport of protein molecules in cells. Therefore, genes involved in the secretory pathway are essential for the cellular development and function. Recent scientific investigations show that ER and Golgi apparatus may provide a convenient drug target for cancer therapy. On the other hand, it is known that abundantly expressed genes in different cellular organelles share interconnected pathways and co-regulate each other activities. The cross-talks among these genes play an important role in signaling pathways, associated to the regulation of intracellular protein transport.ResultsIn the present study, we device an integrated approach to understand these complex interactions. We analyze gene perturbation expression profiles, reconstruct a directed gene interaction network and decipher the regulatory interactions among genes involved in protein transport signaling. In particular, we focus on expression signatures of genes involved in the secretory pathway of MCF7 breast cancer cell line. Furthermore, network biology analysis delineates these gene-centric cross-talks at the level of specific modules/sub-networks, corresponding to different signaling pathways.ConclusionsWe elucidate the regulatory connections between genes constituting signaling pathways such as PI3K-Akt, Ras, Rap1, calcium, JAK-STAT, EFGR and FGFR signaling. Interestingly, we determine some key regulatory cross-talks between signaling pathways (PI3K-Akt signaling and Ras signaling pathway) and intracellular protein transport.Electronic supplementary materialThe online version of this article (10.1186/s12859-018-2036-2) contains supplementary material, which is available to authorized users.

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“…Moreover, it is increasingly acknowledged that intracellular transport and signaling pathways ( e.g. , PI3K-Akt, EFGR, and FGFR signaling) are interconnected [42] . COPII trafficking was shown to involve in regulating surface levels of receptor tyrosine kinases [43] .…”

“…The hyperactive intracellular transport system may underly the neoplastic phenotypes, including proliferation, migration, and invasion [40,41]. Moreover, it is increasingly acknowledged that intracellular transport and signaling pathways (e.g., PI3K-Akt, EFGR, and FGFR signaling) are interconnected [42]. COPII trafficking was shown to involve in regulating surface levels of receptor tyrosine kinases [43].…”

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Fucosyltransferase 4 shapes oncogenic glycoproteome to drive metastasis of lung adenocarcinoma

“…Moreover, it is increasingly acknowledged that intracellular transport and signaling pathways (e.g. PI3K-Akt, EFGR and FGFR signaling) are interconnected 38 .…”