Oncogenic Y-box binding protein-1 as an effective therapeutic target in drug-resistant cancer.
Antineoplastic Agents
/ pharmacology
Cell Nucleus
/ metabolism
Drug Resistance, Neoplasm
/ drug effects
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Gene Regulatory Networks
Humans
Male
Molecular Targeted Therapy
Neoplasms
/ drug therapy
Phosphorylation
/ drug effects
Prognosis
Transcriptional Activation
Y-Box-Binding Protein 1
/ metabolism
Y-box binding protein-1
drug resistance
malignant progression
oncogenic effector
overcoming drug resistance
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
21
01
2019
revised:
13
03
2019
accepted:
18
03
2019
pubmed:
25
3
2019
medline:
18
5
2019
entrez:
24
3
2019
Statut:
ppublish
Résumé
Y-box binding protein-1 (YBX1), a multifunctional oncoprotein containing an evolutionarily conserved cold shock domain, dysregulates a wide range of genes involved in cell proliferation and survival, drug resistance, and chromatin destabilization by cancer. Expression of a multidrug resistance-associated ATP binding cassette transporter gene, ABCB1, as well as growth factor receptor genes, EGFR and HER2/ErbB2, was initially discovered to be transcriptionally activated by YBX1 in cancer cells. Expression of other drug resistance-related genes, MVP/LRP, TOP2A, CD44, CD49f, BCL2, MYC, and androgen receptor (AR), is also transcriptionally activated by YBX1, consistently indicating that YBX1 is involved in tumor drug resistance. Furthermore, there is strong evidence to support that nuclear localization and/or overexpression of YBX1 can predict poor outcomes in patients with more than 20 different tumor types. YBX1 is phosphorylated by kinases, including AKT, p70S6K, and p90RSK, and translocated into the nucleus to promote the transcription of resistance- and malignancy-related genes. Phosphorylated YBX1, therefore, plays a crucial role as a potent transcription factor in cancer. Herein, a novel anticancer therapeutic strategy is presented by targeting activated YBX1 to overcome drug resistance and malignant progression.
Identifiants
pubmed: 30903644
doi: 10.1111/cas.14006
pmc: PMC6500994
doi:
Substances chimiques
Antineoplastic Agents
0
Y-Box-Binding Protein 1
0
YBX1 protein, human
0
Banques de données
GENBANK
['LY294002', 'TAS0612']
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1536-1543Informations de copyright
© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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