Identification of Factors Driving Doxorubicin-Resistant Ewing Tumor Cells to Survival.
Ewing sarcoma
cell resistances
doxorubicin
proteomics
scRNA-seq
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
09 Nov 2022
09 Nov 2022
Historique:
received:
06
10
2022
revised:
26
10
2022
accepted:
03
11
2022
entrez:
26
11
2022
pubmed:
27
11
2022
medline:
27
11
2022
Statut:
epublish
Résumé
Ewing sarcoma (ES) cells exhibit extreme plasticity that contributes to the cell's survival and recurrence. Although multiple studies reveal various signaling pathways mediated by the EWSR1/FLI1 fusion, the specific transcriptional control of tumor cell resistance to doxorubicin is unknown. Understanding the molecular hubs that contribute to this behavior provides a new perspective on valuable therapeutic options against tumor cells. Single-cell RNA sequencing and LC-MS/MS-based quantitative proteomics were used. A goal of this study was to identify protein hubs that would help elucidate tumor resistance which prompted ES to relapse or metastasize. Several differentially expressed genes and proteins, including adhesion, cytoskeletal, and signaling molecules, were observed between embryonic fibroblasts and control and doxorubicin-treated tumor cell lines. While several cancer-associated genes/proteins exhibited similar expression across fibroblasts and non-treated cells, upregulation of some proteins belonging to metabolic, stress response, and growth pathway activation was uniquely observed in doxorubicin-treated sarcoma cells, respectively. The novel information on differentially expressed genes/proteins provides insights into the biology of ES cells, which could help elucidate mechanisms of their recurrence. Collectively, our results identify a novel role of cellular proteins in contributing to tumor cell resistance and escape from doxorubicin therapy and contributing to ES progression.
Sections du résumé
BACKGROUND
BACKGROUND
Ewing sarcoma (ES) cells exhibit extreme plasticity that contributes to the cell's survival and recurrence. Although multiple studies reveal various signaling pathways mediated by the EWSR1/FLI1 fusion, the specific transcriptional control of tumor cell resistance to doxorubicin is unknown. Understanding the molecular hubs that contribute to this behavior provides a new perspective on valuable therapeutic options against tumor cells.
METHODS
METHODS
Single-cell RNA sequencing and LC-MS/MS-based quantitative proteomics were used.
RESULTS
RESULTS
A goal of this study was to identify protein hubs that would help elucidate tumor resistance which prompted ES to relapse or metastasize. Several differentially expressed genes and proteins, including adhesion, cytoskeletal, and signaling molecules, were observed between embryonic fibroblasts and control and doxorubicin-treated tumor cell lines. While several cancer-associated genes/proteins exhibited similar expression across fibroblasts and non-treated cells, upregulation of some proteins belonging to metabolic, stress response, and growth pathway activation was uniquely observed in doxorubicin-treated sarcoma cells, respectively. The novel information on differentially expressed genes/proteins provides insights into the biology of ES cells, which could help elucidate mechanisms of their recurrence.
CONCLUSIONS
CONCLUSIONS
Collectively, our results identify a novel role of cellular proteins in contributing to tumor cell resistance and escape from doxorubicin therapy and contributing to ES progression.
Identifiants
pubmed: 36428591
pii: cancers14225498
doi: 10.3390/cancers14225498
pmc: PMC9688843
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Russian Science Foundation
ID : 21-15-00213
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