CASTOR1 suppresses the progression of lung adenocarcinoma and predicts poor prognosis
Xuefeng Zhou1, Zhenshun Cheng2, Hao Chen1
1Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China.
Abstract:
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.
Insights
CASTOR1, a natural inhibitor of mammalian target of rapamycin (mTOR), is significantly reduced in lung adenocarcinoma. Its restoration suppresses tumor growth and metastasis, suggesting CASTOR1 as a potential therapeutic target for lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- CASTOR1 is a known inhibitor of mammalian target of rapamycin (mTOR).
- Its role in lung adenocarcinoma development is not well understood.
- Reduced CASTOR1 expression is implicated in various human malignancies.
Purpose of the Study:
- To investigate the function of CASTOR1 in lung adenocarcinoma.
- To determine if CASTOR1 expression correlates with clinical parameters and patient survival.
- To elucidate the molecular mechanisms by which CASTOR1 affects lung cancer progression.
Main Methods:
- Analysis of CASTOR1 expression in lung adenocarcinoma cell lines and patient tissues.
- In vitro studies involving ectopic CASTOR1 expression in PC-9 cells.
- Immunohistochemistry, immunoblotting, and quantitative reverse transcription PCR.
- Correlation analysis with clinical data (smoking history, TNM stage, metastasis) and survival analysis (Kaplan-Meier).
- Biochemical assays to assess mTOR and S6K phosphorylation.
Main Results:
- CASTOR1 expression was significantly lower in lung adenocarcinoma cells and tissues compared to normal controls.
- Ectopic CASTOR1 expression inhibited proliferation, migration, and invasion of lung cancer cells.
- Low CASTOR1 levels correlated negatively with smoking history, advanced TNM stage, lymph node, and distant metastasis.
- Patients with high CASTOR1 expression had a better 5-year survival rate.
- CASTOR1 suppressed mTOR and downstream S6K phosphorylation.
Conclusions:
- CASTOR1 acts as a tumor suppressor in lung adenocarcinoma.
- CASTOR1 inhibits lung tumorigenesis by regulating mTOR signaling.
- CASTOR1 may serve as a prognostic marker and potential therapeutic target for lung adenocarcinoma.
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