Lipid rafts are specialized membrane microdomains enriched in cholesterol and sphingolipids thought to act as dynamic signalling and sorting platforms. Given their fundamental roles in cellular regulation, there is a plethora of information on the size, composition and regulation of these membrane microdomains, including a large number of proteomics studies. To facilitate the mining and analysis of published lipid raft proteomics studies, first we have developed a searchable database RaftProt. Currently it hosts information about 117 proteomes derived from 69 different cell and tissue types across six mammalian species. In addition to variety of different search and browse features, we have captured the lipid raft preparation methods and implemented advanced search option for methodology and sample treatment conditions, such as cholesterol depletion. Furthermore, we have identified a list of high confidence proteins, and enabled searching only from this list of likely bona fide lipid raft proteins. Secondly, with the aim to identify of a common mechanism for lipid raft-mediated tumor progression, we integrated subcellular proteomics with computational systems biology approach. For this, we identified ‘core cancer raft proteins’ by analysing rafts from ovarian cancer, prostate cancer, breast cancer, renal cell carcinoma and melanoma which may offer novel pan-cancer therapeutic targets/strategies. Our analysis suggest that the proteins from cancer rafts have enhanced tendency to engage in protein-protein interactions, leading to much larger and more-dense interaction networks. Moreover, we observed strong enrichment of cytoskeletal assemblies in the membrane rafts during cancer progression which was abrogated by tumor suppressors OPCML and PTRF in epithelial ovarian cancer and prostate cancer respectively. Taken together, our results demonstrate the value of integrative computational analysis of subcellular proteomics data in biomedical research.