Détail du document
Identifiant
doi:10.1038/s41419-024-06451-w...
Auteur
Gui, Yanping Qian, Xiaoping Ding, Youxiang Chen, Qianqian Fangyu Ye Ye, Yuting Hou, Yingjian Yu, Jun Zhao, LiLangue
enEditeur
Nature
Catégorie
Life Sciences
Année
2024
Date de référencement
24/01/2024
Mots clés
stemness phosphorylation nanog cancer c-fos colonRésumé
Acquired drug resistance is one of the most common limitations for the clinical response of colon cancer to 5-Fluorouracil (5-FU)-based chemotherapy.
The relevant molecular mechanisms might be diversity, but still not be elucidated clearly.
In this study, we aimed to investigate the potential mechanisms of c-Fos, a subfamily of activator protein-1, in 5-FU chemoresistance.
We determined that phosphorylated c-Fos promoted colon cancer cells resistance to 5-FU by facilitating the cancer stemness.
Mechanically, 5-FU treatment induced autolysosome-dependent degradation of TMPO, which subsequently triggered ERK-mediated phosphorylation of c-Fos.
Additionally, c-Fos was found to bind to the promoter of NANOG and phosphorylation of c-Fos at Ser 374 was required for its regulation of NANOG expression.
NANOG ablation impaired c-Fos/p-c-Fos induced 5-FU resistance and stemness.
Taken together, these findings revealed that TMPO-mediated phosphorylation of c-Fos conferred 5-FU resistance by regulating NANOG expression and promoting cell stemness in colon cancer cells.
c-Fos could be as a therapeutic target for colon cancer.
Gui, Yanping,Qian, Xiaoping,Ding, Youxiang,Chen, Qianqian,Fangyu Ye,Ye, Yuting,Hou, Yingjian,Yu, Jun,Zhao, Li, 2024, c-Fos regulated by TMPO/ERK axis promotes 5-FU resistance via inducing NANOG transcription in colon cancer, Nature
Projection-Specific Heterogeneity of the Axon Initial Segment of Pyramidal Neurons in the Prelimbic Cortex
heterogeneity projection-specific
