FOLFOX Therapy Induces Feedback Upregulation of CD44v6 through YB-1 to Maintain Stemness in Colon Initiating Cells.
ATP Binding Cassette Transporter, Subfamily B
/ genetics
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Biomarkers
CRISPR-Cas Systems
Cell Differentiation
Cell Self Renewal
/ genetics
Colonic Neoplasms
/ drug therapy
Drug Resistance, Neoplasm
/ genetics
Fluorouracil
/ therapeutic use
Gene Expression Profiling
Gene Knockout Techniques
Humans
Hyaluronan Receptors
/ genetics
Immunophenotyping
Leucovorin
/ therapeutic use
Neoplastic Stem Cells
/ drug effects
Organoplatinum Compounds
/ therapeutic use
Signal Transduction
Y-Box-Binding Protein 1
/ metabolism
CD44v6
CD44v6 CRISPR/Cas9 knockout
CD44v6-therapy
CIC
MDR1
YB-1
YB-1 CRISPR/Cas9 knockout
colorectal cancer (CRC)
stemness genes
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
13 Jan 2021
13 Jan 2021
Historique:
received:
16
12
2020
revised:
04
01
2021
accepted:
09
01
2021
entrez:
16
1
2021
pubmed:
17
1
2021
medline:
10
4
2021
Statut:
epublish
Résumé
Cancer initiating cells (CICs) drive tumor formation and drug-resistance, but how they develop drug-resistance characteristics is not well understood. In this study, we demonstrate that chemotherapeutic agent FOLFOX, commonly used for drug-resistant/metastatic colorectal cancer (CRC) treatment, induces overexpression of CD44v6, MDR1, and oncogenic transcription/translation factor Y-box-binding protein-1 (YB-1). Our study revealed that CD44v6, a receptor for hyaluronan, increased the YB-1 expression through PGE2/EP1-mTOR pathway. Deleting CD44v6, and YB-1 by the CRISPR/Cas9 system attenuates the in vitro and in vivo tumor growth of CICs from FOLFOX resistant cells. The results of DNA:CD44v6 immunoprecipitated complexes by ChIP (chromatin-immunoprecipitation) assay showed that CD44v6 maintained the stemness traits by promoting several antiapoptotic and stemness genes, including
Identifiants
pubmed: 33451103
pii: ijms22020753
doi: 10.3390/ijms22020753
pmc: PMC7828641
pii:
doi:
Substances chimiques
ABCB1 protein, human
0
ATP Binding Cassette Transporter, Subfamily B
0
Biomarkers
0
CD44v6 antigen
0
Hyaluronan Receptors
0
Organoplatinum Compounds
0
Y-Box-Binding Protein 1
0
YBX1 protein, human
0
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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