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Fbxo6 confers drug-sensitization to cisplatin via inhibiting the activation of Chk1 in non-small cell lung cancer.
- Source :
-
FEBS letters [FEBS Lett] 2019 Jul; Vol. 593 (14), pp. 1827-1836. Date of Electronic Publication: 2019 Jun 07. - Publication Year :
- 2019
-
Abstract
- Fbxo6 (also called FBG2) is a critical component of the evolutionarily conserved ubiquitin-protein ligase complex SCF (Skp1/Cdc53-Cullin1/F-box). Previous studies have demonstrated that Fbxo6 facilitates the growth and proliferation but inhibits the apoptosis and invasion of gastric cancer cells. However, the role of Fbxo6 in non-small cell lung cancer (NSCLC) is still not clear. Our results revealed that Fbxo6 expression is correlated with early TNM stage and favorable overall survival of NSCLC patients. Further in vitro experiments showed that Fbxo6 inhibits proliferation, facilitates apoptosis and promotes the sensitivity of cisplatin via decreased expression and phosphorylation of Chk1. Thus, Fbxo6 may be a useful prognosis marker and therapeutic target to overcome the chemoresistance of cisplatin-based chemotherapy agents in NSCLC patients.<br /> (© 2019 Federation of European Biochemical Societies.)
- Subjects :
- A549 Cells
Aged
Aged, 80 and over
Apoptosis drug effects
Carcinoma, Non-Small-Cell Lung diagnosis
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung pathology
Cell Proliferation drug effects
Enzyme Activation drug effects
Female
Gene Knockdown Techniques
Humans
Lung Neoplasms diagnosis
Lung Neoplasms genetics
Lung Neoplasms pathology
Male
Neoplasm Staging
Prognosis
SKP Cullin F-Box Protein Ligases deficiency
SKP Cullin F-Box Protein Ligases genetics
Thiophenes pharmacology
Urea analogs & derivatives
Urea pharmacology
Carcinoma, Non-Small-Cell Lung metabolism
Checkpoint Kinase 1 metabolism
Cisplatin pharmacology
Drug Resistance, Neoplasm
Lung Neoplasms metabolism
SKP Cullin F-Box Protein Ligases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3468
- Volume :
- 593
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- FEBS letters
- Publication Type :
- Academic Journal
- Accession number :
- 31140586
- Full Text :
- https://doi.org/10.1002/1873-3468.13461