Knock-down of PSAT1 Enhances Sensitivity of NSCLC Cells to Glutamine-limiting Conditions

Anticancer Res. 2019 Dec;39(12):6723-6730. doi: 10.21873/anticanres.13887.

Abstract

Background/aim: 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: 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: 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: Inhibiting PSAT1 might aid in the treatment of lung cancer, and PSAT1 may be a therapeutic target for lung cancer.

Keywords: Activating transcription factor 4; glutamine; ionizing radiation; non-small cell lung cancer; phosphoserine aminotransferase 1.

MeSH terms

  • Activating Transcription Factor 4 / metabolism
  • Benzeneacetamides / pharmacology
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Cell Line, Tumor
  • Cell Survival
  • Gene Knock-In Techniques
  • Glutaminase / antagonists & inhibitors
  • Glutamine / antagonists & inhibitors
  • Glutamine / metabolism*
  • Humans
  • Lung / metabolism
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy
  • RNA, Messenger / metabolism
  • Radiation Tolerance
  • Thiadiazoles / pharmacology
  • Transaminases / genetics
  • Transaminases / metabolism*

Substances

  • ATF4 protein, human
  • Benzeneacetamides
  • CB-839
  • RNA, Messenger
  • Thiadiazoles
  • Glutamine
  • Activating Transcription Factor 4
  • Transaminases
  • phosphoserine aminotransferase
  • Glutaminase