Phospho-proteomic Analysis of Neuroblastoma Tumor Initiating Cell Signaling Pathways: Identification of Src Family and B Cell Receptor Signaling as Novel Drug Targets
Year: 2010
Type: dissertation
Abstract: Neuroblastoma (NB) is the most common extra-cranial solid tumor in children. Recently \ndiscovered neuroblastoma tumor-initiating cells (NB-TICs) have many properties of cancer stem \ncells and form tumors with as few as 10 cells. To elucidate the signaling pathways driving NB- \nTIC survival and proliferation, we surveyed the phospho-tyrosine containing subset of the NB- \nTIC proteome. Over 300 phosphorylated proteins were identified, including 21 tyrosine kinases \nof which several belong to the Src kinase family. Using bioinformatics tools, several \nhematopoietic signaling pathways were identified, including the B cell receptor (BCR) pathway. Further proteomic approaches substantiated molecular hematopoietic features in NB-TICs. \nInhibitors of BCR proximal kinases SYK and SFKs were cytotoxic to NB-TICs. Clinically \nutilized inhibitors of SFKs induce apoptosis in NB-TICs. Targeting hematopoietic survival \npathways in NB-TICs from the bone marrow, which have thus far not been predicted to play a role in this neural malignancy, may provide new drug therapies for NB.
Source: TSpace (University of Toronto)
Author: Milijana Vojvodic
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2763039530