title: Coiled-coil domain-containing protein 8 inhibits the invasiveness and migration of non-small cell lung cancer cells.
abstract: Lung cancer has always been the leading cause of death among patients with malignant tumors, and the majority of these patients die because of cancer cell invasion and metastasis. Previous studies have implicated coiled-coil domain-containing protein 8 (CCDC8) as a tumor suppressor in several types of cancer, such as breast and prostate cancers. However, the expression levels or functions of CCDC8 in lung cancer have not been elucidated. Here, we used immunohistochemical staining to measure CCDC8 expression in 147 samples from tumors and 30 samples from the adjacent normal lung tissues of patients with non-small cell lung cancer. CCDC8 was shown to be located predominantly in the cytoplasm and partially on the cell membrane, and its expression level was significantly lower in lung cancer samples than that in the adjacent normal lung tissues (P=.001). CCDC8 expression was closely related to tumor differentiation (P=.039), tumor-node-metastasis stage (P=.009), lymph node metastasis (P=.038), and prognosis (P=.043) of lung cancer. Transfection of A549 cells with CCDC8 significantly reduced cell invasion and migration (P<.05), whereas the invasiveness and migration capacity in CCDC8-knockdown A549 cells were significantly increased in comparison with the control cells (P<.05). Furthermore, we demonstrated that CCDC8 can downregulate the expression of Snail and upregulate the expression of E-cadherin by inhibiting p-P38 and p-IκBα. Collectively, CCDC8 may suppress the invasion and metastasis of lung cancer cells, and it may represent a promising therapeutic target for non-small cell lung cancer.
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110001, China.
authors.forename: Gui-Yang
authors.initials: GY
authors.lastname: Jiang
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110001, China.
authors.forename: Xiu-Peng
authors.initials: XP
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Cancer Hospital of China Medical University, Shenyang 110042, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110001, China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Xu
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110001, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110001, China. Electronic address: liqingch@hotmail.com.
authors.forename: Qing-Chang
authors.initials: QC
authors.lastname: Li
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110001, China.
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000556:secondary / Q000628:therapy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D034622:RNA Interference; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C569196:CCDC8 protein, human; C513384:CDH1 protein, human; D015820:Cadherins; D002352:Carrier Proteins; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000071250:Snail Family Transcription Factors; D025521:Tumor Suppressor Proteins; D000072000:NF-KappaB Inhibitor alpha; C496559:CHUK protein, human; D051550:I-kappa B Kinase; D048051:p38 Mitogen-Activated Protein Kinases
keywords: CCDC8; EMT; Invasion; Migration; NSCLC