Proteomics

Dataset Information

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Deep proteomic and phosphoproteomic profiling of neuroblastoma treated with XPO1 inhibitor Selinexor


ABSTRACT: Neuroblastoma accounts for 15% of cancer-related deaths in children, highlighting an unmet need for novel therapies. Selinexor is a small molecule inhibitor of XPO1 that shuffles cargo proteins with a nuclear export sequence, many of which are essential for cancer growth and cell maintenance, from the nucleus to the cytosol. We systematically tested the effect of selinexor against neuroblastoma cells in vitro and in vivo and used a proteomics screening approach to interrogate unknown mechanisms of action. We found that selinexor induces its cytotoxic effects in neuroblastoma through the nuclear accumulation of p53. By combining selinexor with an aurora kinase inhibitor, alisertib that is already in clinical use for neuroblastoma, we show that p53-mediated lethality can be further augmented supporting clinical testing of this drug combination against neuroblastoma

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Neutrophil, Blood

DISEASE(S): Acute Leukemia,Neuroblastoma

SUBMITTER: Hong Wang  

LAB HEAD: Hong Wang

PROVIDER: PXD026454 | Pride | 2023-03-11

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
IDmod_updated.txt Txt
Rosa_Nih_XPO1_hTMTw_phosphoproteome_v01_20210120.xlsx Xlsx
Rosa_Nih_XPO1_hTMTw_proteome_jumpn_rshiny_test.xlsx Xlsx
Rosa_Nih_XPO1_hTMTw_proteome_v01_20210113.xlsx Xlsx
id_uni_pep.txt Txt
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Publications

Combining selinexor with alisertib to target the p53 pathway in neuroblastoma.

Nguyen Rosa R   Wang Hong H   Sun Ming M   Lee Dong Geun DG   Peng Junmin J   Thiele Carol J CJ  

Neoplasia (New York, N.Y.) 20220223


Neuroblastoma accounts for 15% of cancer-related deaths in children, highlighting an unmet need for novel therapies. Selinexor is a small molecule inhibitor of XPO1. XPO1 shuffles cargo proteins with a nuclear export sequence from the nucleus to the cytosol, many of which are essential for cancer growth and cell maintenance. We systematically tested the effect of selinexor against neuroblastoma cells in vitro and in vivo and used an advanced proteomic and phosphoproteomic screening approach to i  ...[more]

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