Abstract
Background: Evidence is emerging that stem cell and systems biology could provide new insights into the design of novel therapeutic strategies for cancer patients. Recent studies indicated that mesenchymal stem cells (MSCs) might play a crucial role in the ability of self-renewal, differentiation, increased membrane transporter activity and the ability to metastasize for cancer cells. It is worth noting that studies have shown that bone marrow-derived MSCs are recruited towards cancer tumors and are thought to be an important microenvironment in the initiation of metastasis. MSCs may not only promote the ability of self-renewal and differentiation of cancer cells, but also be involved in initiation of metastasis of cancer stem cells (CSCs). Cancers are attributable to a large extent to multiple spontaneous and inherited mutations that control central cellular events. There are complicated cross-talks between pathways and biochemical processes that drive the formation and growth of tumors in cancers. As opposed to conventional biology, we apply a systems perspective into the cancerous cells, and systems biology approaches would help us explore how protein-protein interactions (PPIs) and pathways are induced and controlled during the initialization or formation of lung CSCs. In this study, our main goal is to investigate the complex intracellular mechanisms leading to the formation of lung CSCs. Specifically, we seek to study the crucial signaling pathways and possible cross-talks between these pathways that initiate the metastasis or formation of CSCs. Result: Based on MSCs-treated microarray data and Control microarray data, we constructed two intracellular PPI networks. The resulting intracellular MSCs-treated PPI network was comprised of 2586 proteins and 7296 interactions; on the other hand, the intracellular Control PPI network was comprised of 3982 proteins and 11498 interactions. By comparing these two networks, we could find out and predict the role i of the MSCs-secreted factors in the initialization or metastasis of lung CSCs. Our results showed that JAK/STAT pathway might play a crucial role in this setting. Furthermore, we identified STAT3 in our extracted sub-network and crucial proteins, CREBBP, FGFR2, CD44, and NFKB1, were also identified to be pertinent during lung CSCs formation via our centrality analysis. Conclusion: Based on our constructed PPI networks, pathway and centrality analysis, we were able to identify crucial proteins that are highly related to the formation of lung CSCs during treatment of MSCs-secreted factors. We believe that our findings not only provide insights into our comprehension of the formation of CSCs in lung cancers but also shed lights on our path towards better therapeutic strategies for cancer treatment in general.