Advances in membrane proteomics and cancer biomarker discovery: Current status and future perspective

Abstract

Membrane proteomic analysis has been proven to be a promising tool for identifying new and specific biomarkers that can be used for prognosis and monitoring of various cancers. Membrane proteins are of great interest particularly those with functional domains exposed to the extracellular environment. Integral membrane proteins represent about one-third of the proteins encoded by the human genome and assume a variety of key biological functions, such as cell-to-cell communication, receptor-mediated signal transduction, selective transport, and pharmacological actions. More than two-thirds of membrane proteins are drug targets, highlighting their immensely important pharmaceutical significance. Most plasma membrane proteins and proteins from other cellular membranes have several PTMs; for example, glycosylation, phosphorylation, and nitrosylation, and moreover, PTMs of proteins are known to play a key role in tumor biology. These modifications often cause change in stoichiometry and microheterogeneity in a protein molecule, which is apparent during electrophoretic separation. Furthermore, the analysis of glyco- and phosphoproteome of cell membrane presents a number of challenges mainly due to their low abundance, their large dynamic range, and the inherent hydrophobicity of membrane proteins. Under pathological conditions, PTMs, such as phosphorylation and glycosylation are frequently altered and have been recognized as a potential source for disease biomarkers. Thus, their accurate differential expression analysis, along with differential PTM analysis is of paramount importance. Here we summarize the current status of membrane-based biomarkers in various cancers, and future perspective of membrane biomarker research.

Optimized Approaches for Quantification of Drug Transporters in Tissues and Cells by MRM Proteomics

“…A number of research and review papers covering selective elements of transporter quantification by MRM have been published [16,[27][28][29][30]. Here, we have synthesized these elements to provide a step-by-step guide to develop reliable transporter quantification methods in tissues or cell lines with emphasis on following steps: (i) surrogate peptide selection, (ii) peptide qualification, (iii) peptide synthesis and characterization, (iv) membrane protein isolation, (v) protein digestion, (vi) sample preparation, (vii) LC-MS/MS parameter optimization, (viii) method validation, and (ix) sample analysis (Fig.…”

Integrated proteo-genomic approach for early diagnosis and prognosis of cancer

“…Cellular signaling is largely controlled by transient, PTMs of signaling proteins, which alter their ability to bind and interact with downstream effectors. Protein phosphorylation is one such modification that primarily acts as a molecular switch to activate or deactivate cellular signaling cascades [18]. The study of PTMs as a source of biomarkers in cancer is still at a relatively early stages.…”

“…Identification of membrane proteins with aberrant properties can result in discovery of novel therapeutic targets for most membrane proteins, receptor activities of their extracellular domains are often mediated via Nlinked glycosylation, whereas the cytoplasmic domains can be phosphorylated reversiblyand function as signal transducers[18] (Fig. 1).…”

An effective and in-situ method based tresyl-functionalized porous polymer material for enrichment and digestion of membrane proteins and its application in extraction tips

“…These evidence strongly suggest MPs as an interesting molecular targets for drug discovery. Hence, studying the biological activities of MPs can facilitate us with deep insight into their roles in a cell or tissue, thereby to find a novel therapeutic way to treat the disease [2,3]. However, the identification of MPs is still puzzled by their low abundance in biomass, large molecular weight and poor solubility in aqueous solution [4,5].…”