Boundary Spaces:Behaviour and Semantics of Membrane Transport in Human Cancer

Cancer cells are markedly different from their healthy counterparts. During tumorigenesis, the complex system of the cell, which operates on a different organizational layer than the organism, modifies its regulatory mechanism and begins to disrupt the surrounding tissue. This is due to, specifically, the fact that layer relationships in hierarchical complex systems do not have complete top-down control of their component subsystems. It is clear how tumorigenesis modifies the nature and behaviour of cancer cells. However, which aspects of the cell-system that underline these changes are yet not completely clear. We analyse one thin aspect of the cell-system that is underappreciated in the literature: the transportome. I develop a novel database built dynamically from remote sources with information regarding membrane transporters. This database, named Membrane Transport Protein Database, is shared with an open license, can be updated quickly and easily and handles a lot of the complexity present in the remote databases. With a novel algorithm, I create unbiased gene lists based on the characteristics of the transporters in question. Combining these lists with gene expression data from The Cancer Genome Atlas and the Genotype-Tissue Expression consortia, as well as independent GEO studies, the Gene Set Enrichment Analysis approach highlighted a general downregulation of channels in most tumor types, with the associated upregulation of some pumps, especially proton pumps. These findings confirm previous preliminary observations and expand the scope of inquiry to all cancer types, enabling further analyses and experimental approaches. I highlight the role of data and computational reproducibility in supporting the statements I presented above, and expand this discussion to all data-intensive biological studies. I finally propose a new conceptualization of the transporters that takes into account more completely the role of the transporter as tiny complex systems that provide the function of molecular transporters. This work will hopefully stimulate further progress in the study of the transportome in a rigorous and reproducible way