Pharmacological targeting of the novel β-catenin chromatin-associated kinase p38α in colorectal cancer stem cell tumorspheres and organoids.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
25 03 2021
25 03 2021
Historique:
received:
06
10
2020
accepted:
01
03
2021
revised:
22
02
2021
entrez:
26
3
2021
pubmed:
27
3
2021
medline:
14
10
2021
Statut:
epublish
Résumé
The prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This is mainly due to drug resistance, recurrence, and subsequent metastatic dissemination, which are sustained by the cancer stem cell (CSC) population. The main driver of the CSC gene expression program is Wnt signaling, and previous reports indicate that Wnt3a can activate p38 MAPK. Besides, p38 was shown to feed into the canonical Wnt/β-catenin pathway. Here we show that patient-derived locally advanced CRC stem cells (CRC-SCs) are characterized by increased expression of p38α and are "addicted" to its kinase activity. Of note, we found that stage III CRC patients with high p38α levels display reduced disease-free and progression-free survival. Extensive molecular analysis in patient-derived CRC-SC tumorspheres and APC
Identifiants
pubmed: 33767160
doi: 10.1038/s41419-021-03572-4
pii: 10.1038/s41419-021-03572-4
pmc: PMC7994846
doi:
Substances chimiques
Chromatin
0
beta Catenin
0
Mitogen-Activated Protein Kinase 14
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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