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

• Published in: Anticancer research 2019-12, Vol.39 (12), p.6723-6730
• Main Authors: Jin, Hyeon-Ok, Hong, Sung-Eun, Kim, Ji-Young, Jang, Se-Kyeong, Kim, Young-Sun, Sim, Ju-Hee, Oh, Ac-Chin, Kim, Heyjin, Hong, Young Jun, Lee, Jin-Kyung, Park, In-Chul
• Format: Article
• Language: English
• Subjects: Activating transcription factor 4; Activating Transcription Factor 4 - metabolism; Benzeneacetamides - pharmacology; Biosynthesis; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - radiotherapy; Cell Line, Tumor; Cell proliferation; Cell Survival; Constraining; Deprivation; Gene expression; Gene Knock-In Techniques; Glutaminase - antagonists & inhibitors; Glutamine; Glutamine - antagonists & inhibitors; Glutamine - metabolism; Humans; Ionizing radiation; Lung - metabolism; Lung cancer; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - radiotherapy; Non-small cell lung carcinoma; Phosphoserine; Phosphoserine aminotransferase; Polymerase chain reaction; Radiation effects; Radiation Tolerance; Reverse transcription; RNA, Messenger - metabolism; Sensitivity enhancement; Serine; Small cell lung carcinoma; Therapeutic applications; Thiadiazoles - pharmacology; Transaminases - genetics; Transaminases - metabolism; Viability
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.13887

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.