Exosomal protein interactors as emerging therapeutic targets in urothelial bladder cancer.
BACKGROUND
Exosomes are rich sources of biological material (proteins and nucleic acids) secreted by both tumor and normal cells, and found in urine of urinary bladder cancer patients.


OBJECTIVE
The objective of the study was to identify interacting exosomal proteins in bladder cancer for future use in targeted therapy.


METHODS
The Exocarta database (www.exocarta.org) was mined for urinary bladder cancer specific exosomal proteins. The urinary bladder cancer specific exosomal proteins (n=248) were analyzed to identify enriched pathways by Onto-tool Pathway Express (http://vortex.cs.wayne.edu/ontoexpress).


RESULTS
Enriched pathways included cellular architecture, motility, cell to cell adhesion, tumorigenesis and metastasis. Proteins in the 9 top-ranked pathways included CTNNA1 (alpha-catenin), CTNNB1 (beta-catenin), VSAP, ITGA4, PAK1, DDR1, CDC42, RHOA, NRAS, RHO, PIK3AR1, MLC1, MMRN1, and CTTNBP2 and network analysis revealed 10 important hub proteins and identified inferred interactor NF2.


CONCLUSIONS
The importance of identifying interactors is that that they can be used as targets for therapy, for example, using Bevacizumab (avastin--an angiogenesis inhibitor) against NF2 to inhibit protein-protein interactions will inhibit tumor growth and progression by hindering the exosome biogenesis.
National Institute of Pathology, Indian Council of Medical Research, New Delhi 110029, India. Electronic address: nitu86mishra@gmail.com.
Nitu
N
Kumari
National Institute of Pathology, Indian Council of Medical Research, New Delhi 110029, India.
Sunita
S
Saxena
National Institute of Pathology, Indian Council of Medical Research, New Delhi 110029, India. Electronic address: uburra@yahoo.com.
Usha
U
Agrawal
D019295:Computational Biology; D030562:Databases, Protein; D055354:Exosomes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D011485:Protein Binding; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D015398:Signal Transduction; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism*
Exosome; Urinary bladder cancer