PMID- 30132978 OWN - NLM STAT- MEDLINE DCOM- 20191125 LR - 20191210 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 119 IP - 12 DP - 2018 Dec TI - CASTOR1 suppresses the progression of lung adenocarcinoma and predicts poor prognosis. PG - 10186-10194 LID - 10.1002/jcb.27360 [doi] AB - 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. CI - (c) 2018 Wiley Periodicals, Inc. FAU - Zhou, Xuefeng AU - Zhou X AD - Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China. FAU - Cheng, Zhenshun AU - Cheng Z AD - Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Chen, Hao AU - Chen H AD - Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China. FAU - Shi, Shenqi AU - Shi S AD - Department of Surgery, Dawu People's Hospital, China. FAU - Wang, Xianguo AU - Wang X AD - Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China. FAU - Orang, Matthew AU - Orang M AD - Department of Physical Education & Human Performance, Central Connecticut State University, New Britain, Connecticut. FAU - Zhao, Jinping AU - Zhao J AUID- ORCID: 0000-0002-4699-6240 AD - Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China. LA - eng PT - Journal Article DEP - 20180821 PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (CASTOR1 protein, human) RN - 0 (Carrier Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) SB - IM MH - Adenocarcinoma of Lung/*genetics/pathology MH - Aged MH - Carcinogenesis/*genetics MH - Carrier Proteins/*genetics MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - Disease Progression MH - Disease-Free Survival MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Intracellular Signaling Peptides and Proteins MH - Kaplan-Meier Estimate MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - Neoplasm Invasiveness/genetics/pathology MH - Neoplasm Staging MH - *Prognosis MH - Signal Transduction OTO - NOTNLM OT - CASTOR1 OT - lung adenocarcinoma OT - mammalian target of rapamycin OT - proliferation EDAT- 2018/08/23 06:00 MHDA- 2019/11/26 06:00 CRDT- 2018/08/23 06:00 PHST- 2017/11/25 00:00 [received] PHST- 2018/06/26 00:00 [accepted] PHST- 2018/08/23 06:00 [pubmed] PHST- 2019/11/26 06:00 [medline] PHST- 2018/08/23 06:00 [entrez] AID - 10.1002/jcb.27360 [doi] PST - ppublish SO - J Cell Biochem. 2018 Dec;119(12):10186-10194. doi: 10.1002/jcb.27360. Epub 2018 Aug 21.