Proteomic Technology “Lens” for Epithelial-Mesenchymal Transition Process Identification in Oncology (original) (raw)
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EuPA Open Proteomics, 2016
The growing understanding of the molecular mechanisms underlying epithelial-to-mesenchymal transition (EMT) may represent a potential source of clinical markers. Despite EMT drivers have not yet emerged as candidate markers in the clinical setting, their association with established clinical markers may improve their specificity and sensitivity. Mass spectrometry-based platforms allow analyzing multiple samples for the expression of EMT candidate markers, and may help to diagnose diseases or monitor treatment efficiently. This review highlights proteomic approaches applied to elucidate the differences between epithelial and mesenchymal tumors and describes how these can be used for target discovery and validation.
Journal of Translational Medicine, 2022
Epithelial–mesenchymal transition (EMT) is a dynamic and complex cellular process that is known to be hijacked by cancer cells to facilitate invasion, metastasis and therapeutic resistance. Several quantitative measures to assess the interplay between EMT and cancer progression are available, based on large scale genome and transcriptome data. However, these large scale multi-omics studies have repeatedly illustrated a lack of correlation in mRNA and protein abundances that may be influenced by diverse post-translational regulation. Hence, it is imperative to understand how changes in the EMT proteome are associated with the process of oncogenic transformation. To this effect, we developed a parallel reaction monitoring-based targeted proteomics method for quantifying abundances of EMT-associated proteins across cancer cell lines. Our study revealed that quantitative measurement of EMT proteome which enabled a more accurate assessment than transcriptomics data and revealed specific ...
Molecular bioSystems, 2012
The epithelial to mesenchymal transition (EMT) is a cellular program associated with the organ morphogenesis but also with the disease progression. EMT in the cancer field fuels neoplastic progression promoting the resistance to cell death, the resistance to chemotherapy and the acquisition of stem cell properties. Considering the crucial role of EMT in breast cancer metastasis, a better understanding of this process may provide new therapeutic options. Here, by using a proteomic approach we identified a set of proteins differentially expressed between an epithelial and a mesenchymal breast cancer cell line. The protein-protein network of these identified proteins was determined by an in silico analysis highlighting, in the EMT program, the role of proteins involved in cell adhesion, migration, and invasion, together with protein kinases involved in proliferation and survival, with many of these emerging as possible targets of novel biological agents. Finally, the pharmacological inhibition of some of these kinases was able to reverse the mesenchymal phenotype to an epithelial phenotype.
The molecular make-up of a tumour: proteomics in cancer research
Clinical Science, 2005
The enormous progress in proteomics, enabled by recent advances in MS (mass spectrometry), has brought protein analysis back into the limelight of cancer research, reviving old areas as well as opening new fields of study. In this review, we discuss the basic features of proteomic technologies, including the basics of MS, and we consider the main current applications and challenges of proteomics in cancer research, including (i) protein expression profiling of tumours, tumour fluids and tumour cells; (ii) protein microarrays; (iii) mapping of cancer signalling pathways; (iv) pharmacoproteomics; (v) biomarkers for diagnosis, staging and monitoring of the disease and therapeutic response; and (vi) the immune response to cancer. All these applications continue to benefit from further technological advances, such as the development of quantitative proteomics methods, high-resolution, high-speed and high-sensitivity MS, functional protein assays, and advanced bioinformatics for data hand...
Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti
Background: Cancer metastasis involves changes in signalling pathways, cell adhesion, migra tion and invasiveness. Modern proteomic, mass spectrometry based techniques enable disco very of new prometastatic proteins and their functional partners. Also, they might be involved in their functional characterisation and validation towards development of new diagnostic and therapeutic approaches. Aim: The aim of this communication is to describe current possibili ties for proteomic techniques in the discovery and characterization of prometastatic targets. The NFκB pathway is one of the players responsible for a number of prometastatic processes. The related proteins can be discovered using untargeted proteomic approaches by compa ring proteomes with different metastatic potential. Stable isotope labelling based methods enable a parallel analysis of more tumour samples. The identified prometastatic proteins can be characterised in relationship to cell migration, invasiveness and proliferation and in terms of their involvement in molecular complexes via proteinprotein interactions. Advan tages of the metabolic labelling based methods can be taken in these studies, the same ap plies for chara cterisation of related surface proteins involved in cell adhesion, invasiveness and celltocell communication. For clinical validation of prometastatic proteins in large sample cohorts, approaches of targeted proteomics based on selected reaction monitoring are becom ing methods of choice. Conclusion: Current proteomics methods play an important role in the identification of novel prometastatic proteins, pathways and molecular complexes, in their functional characterisation and validation towards diagnostic and therapeutic application.
Proteomic Strategies and their Application in Cancer Research
Tumori Journal, 2005
T he publication of genome sequences from several organisms is an important recent advance; however, the benefits derived from this information can only be obtained when the spatial and temporal expression, function, and interactions of the gene products are known. With very few exceptions, these gene products are proteins, and although RNA and DNA microarrays can be used to detect gene expression in cells and tissues, these techniques cannot be used for the analysis of biological fluids. Furthermore, the intracellular location, posttranslational modifications, and protein-protein interactions can only be analyzed at the protein level. Thus there is considerable interest in the rapidly expanding field of proteomics, which can be defined as the analysis of the spatial and temporal expression of a subset (and ultimately a full set) of proteins in a defined biological system. Significant recent contributions have focused on use of iterative glutathione-S-transferase fusion probes (1) and tandem affinity purification strategies for discovery of protein interactions. Additional major efforts involve studies of protein machines and organelles (3). Analysis of protein-protein interactions and posttranslational modification in a "multiplex" or global manner is also a part of proteomics. The hallmarks of proteomics reside in its emphasis on taking a global and comprehensive view, involving in many cases some notion of "high throughput"; but in contrast to genomics, there is not a single biochemical method that can be used for the analysis of all proteins. This is due to the obvious fact that the chemistry of proteins involves physicochemical properties that can affect the composition of all individual macromolecules comprising a living system, whereas that of nucleic acids is uniform. Also, no equivalent for the polymerase chain reaction is available for proteins. Therefore, the choice of analytical methods used to visualize the proteome(s) under study does, in fact, influence the subset of proteins that will be identified. Therefore, our aim is to summarize the most important of these methods that are currently available to the researcher and to highlight their strengths and weaknesses, particularly in the context of investigating kidney function. Advances in technological and mass spectrometric methods, such as electrophoresis, electrospray ionization (ESI), and matrix-assisted laser desorption/ionization (MALDI), which are the subject of intense current research and development, will not be discussed.
Biomedical Research Journal
With the emergence of the field of 'omics' a new era of systematic global profiling of cellular molecules has been initiated in biology. Different 'omics' approaches have been extensively used to identify biomarkers for better diagnosis and prognosis, therapeutic strategies and monitoring response to therapy in diverse types of cancers. Proteomics is the approach of choice for identification of therapeutic targets. This is because therapeutic modulation of expression, post-translational modification and activity of a protein can directly rectify the derangement in the disease-causing cellular pathway. The current review scans literature on tumor proteomics to understand the influence of developments in proteomics technology and study approaches on identification of targets for therapy. Diversity of tumor types, molecular heterogeneity in pathologically indistinguishable tumors provides ample challenge to assess the strength of proteomics in identification of drug targets. The review highlights comparative proteomic profiling by gel-based or gel free approach, in tumor and normal tissues or chemo-resistant/sensitive tumor tissues have identified differentiator proteins, with potential as targetsas therapeutic targets. Further, along with evolution in proteomic technologies for identification and quantification of proteins, various tools for functional analysis of proteins have contributed to strategies for target identification. It also suggests that future advances in quantitative, functional and structural proteomics isare necessary to widen the search for therapeutic targets.
Proteome analysis and its impact on the discovery of serological tumor markers
Clinica chimica acta, 2001
Background: Proteomics is a rapidly growing field of research that is becoming increasingly important as we enter the post-genome era. Remarkable improvements in the technologies of high-resolution two-dimensional polyacrylamide gel Ž . Ž . electrophoresis 2D PAGE and mass spectrometry MS have marked the start of proteome analysis and its application to the study of human diseases. Besides studying the proteins involved in carcinogenesis, it is also applicable to the discovery of serological tumor markers for clinical uses, such as for hepatocellular carcinoma. Conclusions: The combination of 2D PAGE and MS is the most widely used technique for proteomics, although other more automated high-throughput techniques are being developed. q .hk P.J. Johnson . 0009-8981r01r$ -see front matter q 2001 Elsevier Science B.V. All rights reserved.
Proteomic strategies and challenges in tumor metastasis research
Clinical & Experimental Metastasis, 2010
The rapidly evolving field of proteomics offers new approaches to understanding the pathogenesis of cancer and metastatic disease. Although numerous tumor markers have been identified with different genomic methods in the past, most are either not specific or sensitive enough to be used in routine clinical setting. The rationale for proteomic profiling is based on the fact that proteins represent the dynamic state of the cells, reflecting pathophysiological changes in the disease more accurately than genomic and epigenetic alterations. Emerging proteomic techniques allow simultaneous assessment of a large number of proteins at one time. The study of protein profiles in complex systems, such as plasma, serum or tissues of cancer patients is likely to become valuable for monitoring the response of patients during treatment or for detecting recurrence of the disease.
Proteomics in human cancer research
PROTEOMICS – Clinical Applications, 2007
Proteomics is now widely employed in the study of cancer. Many laboratories are applying the rapidly emerging technologies to elucidate the underlying mechanisms associated with cancer development, progression, and severity in addition to developing drugs and identifying patients who will benefit most from molecular targeted compounds. Various proteomic approaches are now available for protein separation and identification, and for characterization of the function and structure of candidate proteins. In spite of significant challenges that still exist, proteomics has rapidly expanded to include the discovery of novel biomarkers for early detection, diagnosis and prognostication (clinical application), and for the identification of novel drug targets (pharmaceutical application). To achieve these goals, several innovative technologies including 2-D-difference gel electrophoresis, SELDI, multidimensional protein identification technology, isotope-coded affinity tag, solid-state and suspension protein array technologies, X-ray crystallography, NMR spectroscopy, and computational methods such as comparative and de novo structure prediction and molecular dynamics simulation have evolved, and are being used in different combinations. This review provides an overview of the field of proteomics and discusses the key proteomic technologies available to researchers. It also describes some of the important challenges and highlights the current pharmaceutical and clinical applications of proteomics in human cancer research.