Role of the stem cell-associated intermediate filament nestin in malignant proliferation of non-small cell lung cancer

• Published in: PloS one Vol. 9; no. 2; p. e85584
• Main Authors: Chen, Zhenguang, Wang, Jiancheng, Cai, Lie, Zhong, Beilong, Luo, Honghe, Hao, Yuantao, Yu, Weihua, Wang, Binchao, Su, Chunhua, Lei, Yiyan, Bella, Amos Ela, Xiang, Andy Peng, Wang, Tao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.02.2014; Public Library of Science (PLoS)
• Subjects: AKT protein; Biology; Biotechnology; Cancer; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation; Education; Female; G1 Phase Cell Cycle Checkpoints - genetics; Gene Expression Regulation, Neoplastic; Glycogen Synthase Kinase 3 - metabolism; Hospitals; Humans; Immunoblotting; Immunohistochemistry; Inhibition; Intermediate filament proteins; Ki-67 Antigen - metabolism; Kinases; Laboratories; Lung cancer; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Malignancy; Medical prognosis; Medical research; Medicine; Metastasis; Microscopy, Fluorescence; Middle Aged; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Nestin; Nestin - genetics; Nestin - metabolism; Non-small cell lung cancer; Non-small cell lung carcinoma; Prognosis; Proliferating cell nuclear antigen; Proliferating Cell Nuclear Antigen - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Signal transduction; Signaling; Small cell lung cancer; Squamous cell carcinoma; Stem cells; Surgery; Thoracic surgery; Tissue engineering; Transformation; Tumor cell lines; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0085584

Nestin is associated with neoplastic transformation, but the mechanisms by which nestin contributes to invasion and malignancy of lung cancer remain unknown. Considering that proliferation is necessary for malignant behavior, we investigated the mechanism of nestin action in association with the proliferative properties of non-small cell lung cancer (NSCLC). Nestin expression was examined in NSCLC specimens and cell lines. Associations with clinicopathological features, including prognosis and proliferative markers, were evaluated. Effects of nestin knockdown on proliferation and the signaling pathways involved were further investigated. Nestin was expressed in most cancer specimens and all the tumor cell lines analyzed. High nestin expression in malignant tissue was associated with high Ki-67 or PCNA levels and poor patient outcomes. Conversely, knockdown of nestin expression led to significant inhibition of tumor cell proliferation, decreased colony forming ability, and cell cycle G1 arrest. Furthermore, nestin knockdown resulted in inhibition of Akt and GSK3β activation. Our data demonstrate that nestin expression in NSCLC cells is associated with poor prognosis of patients and tumor cell proliferation pathway. Downregulation of nestin efficiently inhibited lung cancer cell proliferation, which might be through affecting cell cycle arrest and Akt-GSK3β-Rb signaling pathway.