Deep-proteome mapping of WM-266-4 human metastatic melanoma cells: From oncogenic addiction to druggable targets

Autor: Aikaterini F. Giannopoulou, Dimitrios J. Stravopodis, Gerassimos E. Voutsinas, Athanasios Anagnostopoulos, Athanassios D. Velentzas, Eumorphia G. Konstantakou, Ourania A. Konstandi, Zoi I. Litou, Ema Anastasiadou, George Th. Tsangaris
Rok vydání: 2016
Předmět:
0301 basic medicine
Melanomas
Proteomics
Skin Neoplasms
Proteome
Fibroblast Growth Factor
Physiology
Carcinogenesis
Proteomes
lcsh:Medicine
Mice
SCID
medicine.disease_cause
Biochemistry
Database and Informatics Methods
Endocrinology
Cell Signaling
Tandem Mass Spectrometry
Medicine and Health Sciences
Protein Interaction Maps
lcsh:Science
Melanoma
Cultured Tumor Cells
Multidisciplinary
Middle Aged
Microphthalmia-associated transcription factor
3. Good health
Neoplasm Proteins
Oncology
Melanoma Cells
Female
Biological Cultures
Signal Transduction
Research Article
Proto-Oncogene Proteins B-raf
Bioinformatics
Biology
Research and Analysis Methods
03 medical and health sciences
Paracrine signalling
Genetic Heterogeneity
Cancer stem cell
Ammonia
Cell Line
Tumor
Growth Factors
medicine
Animals
Humans
KEGG
Melanins
Oncogenic Signaling
Microphthalmia-Associated Transcription Factor
Endocrine Physiology
lcsh:R
Cancers and Neoplasms
Biology and Life Sciences
Proteins
Cell Biology
Cell Cultures
medicine.disease
030104 developmental biology
14-3-3 Proteins
Drug Resistance
Neoplasm
Cutaneous melanoma
Cancer research
lcsh:Q
Propionates
Neoplasm Transplantation
Chromatography
Liquid
Zdroj: PLoS ONE
PLoS ONE, Vol 12, Iss 2, p e0171512 (2017)
ISSN: 1932-6203
Popis: Cutaneous melanoma is a malignant tumor of skin melanocytes that are pigment-producing cells located in the basal layer (stratum basale) of epidermis. Accumulation of genetic mutations within their oncogenes or tumor-suppressor genes compels melanocytes to aberrant proliferation and spread to distant organs of the body, thereby resulting in severe and/or lethal malignancy. Metastatic melanoma's heavy mutational load, molecular heterogeneity and resistance to therapy necessitate the development of novel biomarkers and drug-based protocols that target key proteins involved in perpetuation of the disease. To this direction, we have herein employed a nano liquid chromatography-tandem mass spectrometry (nLC-MS/MS) proteomics technology to profile the deep-proteome landscape of WM-266-4 human metastatic melanoma cells. Our advanced melanoma-specific catalogue proved to contain 6,681 unique proteins, which likely constitute the hitherto largest single cell-line-derived proteomic collection of the disease. Through engagement of UNIPROT, DAVID, KEGG, PANTHER, INTACT, CYTOSCAPE, dbEMT and GAD bioinformatics resources, WM-266-4 melanoma proteins were categorized according to their sub-cellular compartmentalization, function and tumorigenicity, and successfully reassembled in molecular networks and interactomes. The obtained data dictate the presence of plastically inter-converted sub-populations of non-cancer and cancer stem cells, and also indicate the oncoproteomic resemblance of melanoma to glioma and lung cancer. Intriguingly, WM-266-4 cells seem to be subjected to both epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial (MET) programs, with 1433G and ADT3 proteins being identified in the EMT/MET molecular interface. Oncogenic addiction of WM-266-4 cells to autocrine/paracrine signaling of IL17-, DLL3-, FGF(2/13)- and OSTP-dependent sub-routines suggests their critical contribution to the metastatic melanoma chemotherapeutic refractoriness. Interestingly, the 1433G family member that is shared between the BRAF- and EMT/MET-specific interactomes likely emerges as a novel and promising druggable target for the malignancy. Derailed proliferation and metastatic capacity of WM-266-4 cells could also derive from their metabolic addiction to pathways associated with glutamate/ammonia, propanoate and sulfur homeostasis, whose successful targeting may prove beneficial for advanced melanoma-affected patients.
Databáze: OpenAIRE
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