As a naturally occurring inhibitor of mammalian target of rapamycin (mTOR), accumulated evidence has confirmed that CASTOR1 plays a pivotal role in regulating the progression of human malignancies. However, the function of CASTOR1 in the development of lung adenocarcinoma is still unclear. Here we report that the expression of CASTOR1 is significantly reduced in lung adenocarcinoma cell lines as compared with that in normal lung epithelial cells. Cellular studies further revealed that ectopic CASTOR1 expression led to a significant suppression of the cellular proliferation, migration, and invasion of PC-9 cells. To further test the role of CASTOR1 in human patients with lung cancers, tumor tissues derived from lung cancer patients and paired adjacent normal lung tissues were collected for immunohistochemical, biochemical, and molecular biology analysis. Immunoblotting and real-time quantitative reverse transcription polymerase chain reaction analysis is revealed that CASTOR1 was significantly reduced in tumor tissues as compared with that in paired normal lung tissues. With immunostaining and retrospective analysis of pathological samples from lung cancer patients further revealed that expression of CASTOR1 was negatively correlated with smoking history, TNM stage, lymphnode metastasis, and distant metastasis. Furthermore, Kaplan-Meier survival analysis indicated that patients with low CASTOR1 expression levels had a significantly worse 5-year survival rate than those with high CASTOR1 expression. To further explore the molecular actions of CASTOR1 in lung cancer development, biochemical assays were performed and the results suggested that ectopic CASTOR1 expression resulted significant suppression of mTOR and downstream S6K phosphorylation, indicating that CASTOR1 might regulate the progression of lung adenocarcinoma by controlling mTOR activation. Thus, these findings demonstrated that CASTOR1 inhibits the tumorigenesis of lung adenocarcinoma cells and might serve as a potential therapeutic target or prognostic marker for human patients with lung adenocarcinoma.
Keywords: CASTOR1; lung adenocarcinoma; mammalian target of rapamycin; proliferation.
© 2018 Wiley Periodicals, Inc.