Mass spectrometry-based membrane proteomics in cancer biomarker discovery

Abstract

Membrane proteins are involved in central processes such as cell signaling, cell–cell interactions and communication, ion and metabolite transport and in general play a crucial role in cell homeostasis. Cancer and cancer metastasis have been correlated to protein expression levels and dysfunction, with membrane proteins playing an important role, and are thus used as drug targets and potential biomarkers for prognostic or diagnostic purposes. Despite the critical biological significance of membrane proteins, proteomic analysis has been a challenging task due to their hydrophobicity. In this review, recent advances in the proteomic analysis of membrane proteins are presented, focusing on membrane fraction enrichment techniques combined with labeled or label-free shotgun proteomics approaches for the identification of potential cancer biomarkers.

Keywords::

• biomarkers
• cancer
• mass spectrometry
• membrane proteins
• proteomics

Financial & competing interests disclosure

G Mermelekas acknowledges support by FP7 Neurinox (278611). J Zoidakis acknowledges support by Thales Cervicanprot (383418). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Membrane proteins are involved in crucial biological processes.

• The membrane proteome is a significant pool of potential cancer biomarkers.

• Membrane proteins are of low abundance and exhibit intrinsic structural properties.

• Membrane protein enrichment is mandatory prior to proteomics analysis.

• Chaotropes, detergents and organic solvents are used for membrane protein solubilization prior to mass spectrometry proteomics analysis.

• Isolation of plasma membrane proteins can be achieved by centrifugation or cell-surface biotinylation approaches.

• Glycosylation targeted methods have been developed for cell-surface proteins isolation.

• Application of mass spectrometry proteomics has been expanded and used in sub-proteome analysis, such as the membrane proteome in cancer biomarker discovery.

• A variety of potential cancer or metastatic biomarkers have been proposed from membrane proteomic analysis.

Notes