Abstract:
:Hypoxia inducible factor (HIF)-2α protein expression in solid tumors promotes stem-like phenotype in cancer stem cells and increases tumorigenic potential in nonstem cancer cells. Recently, we have shown that HIF-1/2α gene expression is correlated to neuroblastoma (NB) poor survival and to undifferentiated tumor state; HIF-2α protein was demonstrated to enhance aggressive features of the disease. In this study, we used proteomic experiments on NB cells to investigate HIF-2α downstream-regulated proteins or pathways with the aim of providing novel therapeutic targets or bad prognosis markers. We verified that pathways mostly altered by HIF-2α perturbation are involved in tumor progression. In particular, HIF-2α induces alteration of central metabolism and splicing control pathways. Simultaneously, WNT, RAS/MAPK, and PI3K/AKT activity or expression are affected and may impact the sensitivity and the intensity of HIF-2α-regulated pathways. Furthermore, genes coding the identified HIF-2α-related markers built a signature able to stratify NB patients with unfavorable outcome. Taken together, our findings underline the relevance of dissecting the downstream effects of a poor survival marker in developing targeted therapy and improving patient stratification. Future prospective studies are needed to translate the use of these data into the clinical practice.
journal_name
J Proteome Resjournal_title
Journal of proteome researchauthors
Cimmino F,Pezone L,Avitabile M,Persano L,Vitale M,Sassi M,Bresolin S,Serafin V,Zambrano N,Scaloni A,Basso G,Iolascon A,Capasso Mdoi
10.1021/acs.jproteome.6b00457subject
Has Abstractpub_date
2016-10-07 00:00:00pages
3643-3655issue
10eissn
1535-3893issn
1535-3907journal_volume
15pub_type
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