Knock-down of PSAT1 Enhances Sensitivity of NSCLC Cells to Glutamine-limiting Conditions.
Activating Transcription Factor 4
/ metabolism
Benzeneacetamides
/ pharmacology
Carcinoma, Non-Small-Cell Lung
/ metabolism
Cell Line, Tumor
Cell Survival
Gene Knock-In Techniques
Glutaminase
/ antagonists & inhibitors
Glutamine
/ antagonists & inhibitors
Humans
Lung
/ metabolism
Lung Neoplasms
/ metabolism
RNA, Messenger
/ metabolism
Radiation Tolerance
Thiadiazoles
/ pharmacology
Transaminases
/ genetics
Activating transcription factor 4
glutamine
ionizing radiation
non-small cell lung cancer
phosphoserine aminotransferase 1
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
11
11
2019
revised:
16
11
2019
accepted:
18
11
2019
entrez:
8
12
2019
pubmed:
8
12
2019
medline:
18
12
2019
Statut:
ppublish
Résumé
Phosphoserine aminotransferase 1 (PSAT1) is an enzyme implicated in serine biosynthesis, and its overexpression has been linked to cancer cell proliferation. Therefore, targeting PSAT1 is considered to be an anticancer strategy. The viability of non-small cell lung cancer (NSCLC) cells was measured by MTT assay. Protein and mRNA expression were determined by western blot and reverse transcription polymerase chain reaction, respectively. Glutamine-limiting conditions were generated through glutamine deprivation or CB-839 treatment, which induced PSAT1 expression in NSCLC cells. PSAT1 expression induced by glutamine-limiting conditions was regulated by activating transcription factor 4. Knock-down of PSAT1 enhanced the sensitivity of NSCLC cells to glutamine-limiting conditions. Interestingly, ionizing radiation induced PSAT1 expression, and knocking down PSAT1 increased cell sensitivity to ionizing radiation. Inhibiting PSAT1 might aid in the treatment of lung cancer, and PSAT1 may be a therapeutic target for lung cancer.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Phosphoserine aminotransferase 1 (PSAT1) is an enzyme implicated in serine biosynthesis, and its overexpression has been linked to cancer cell proliferation. Therefore, targeting PSAT1 is considered to be an anticancer strategy.
MATERIALS AND METHODS
METHODS
The viability of non-small cell lung cancer (NSCLC) cells was measured by MTT assay. Protein and mRNA expression were determined by western blot and reverse transcription polymerase chain reaction, respectively.
RESULTS
RESULTS
Glutamine-limiting conditions were generated through glutamine deprivation or CB-839 treatment, which induced PSAT1 expression in NSCLC cells. PSAT1 expression induced by glutamine-limiting conditions was regulated by activating transcription factor 4. Knock-down of PSAT1 enhanced the sensitivity of NSCLC cells to glutamine-limiting conditions. Interestingly, ionizing radiation induced PSAT1 expression, and knocking down PSAT1 increased cell sensitivity to ionizing radiation.
CONCLUSION
CONCLUSIONS
Inhibiting PSAT1 might aid in the treatment of lung cancer, and PSAT1 may be a therapeutic target for lung cancer.
Identifiants
pubmed: 31810937
pii: 39/12/6723
doi: 10.21873/anticanres.13887
doi:
Substances chimiques
ATF4 protein, human
0
Benzeneacetamides
0
CB-839
0
RNA, Messenger
0
Thiadiazoles
0
Glutamine
0RH81L854J
Activating Transcription Factor 4
145891-90-3
Transaminases
EC 2.6.1.-
phosphoserine aminotransferase
EC 2.6.1.52
Glutaminase
EC 3.5.1.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6723-6730Informations de copyright
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.