ANLN plays a critical role in human lung carcinogenesis through the activation of RHOA and by involvement in the phosphoinositide 3-kinase/AKT pathway

• Published in: Cancer research (Chicago, Ill.) Vol. 65; no. 24; pp. 11314 - 11325
• Main Authors: SUZUKI, Chie, DAIGO, Yataro, ISHIKAWA, Nobuhisa, KATO, Tatsuya, HAYAMA, Satoshi, ITO, Tomoo, TSUCHIYA, Eiju, NAKAMURA, Yusuke
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.12.2005
• Subjects: Actins - metabolism; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma, Bronchiolo-Alveolar - genetics; Adenocarcinoma, Bronchiolo-Alveolar - metabolism; Adenocarcinoma, Bronchiolo-Alveolar - pathology; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Blotting, Western; Carcinoma, Adenosquamous - genetics; Carcinoma, Adenosquamous - metabolism; Carcinoma, Adenosquamous - pathology; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Movement; Contractile Proteins - genetics; Contractile Proteins - metabolism; Drosophila; Enzyme Activation; Female; Flow Cytometry; Humans; Lung - metabolism; Lung - pathology; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Phosphatidylinositol 3-Kinases - metabolism; Pneumology; Prognosis; Proto-Oncogene Proteins c-akt - metabolism; Reverse Transcriptase Polymerase Chain Reaction; rhoA GTP-Binding Protein - metabolism; RNA, Small Interfering - pharmacology; Signal Transduction; Survival Rate; Tissue Array Analysis; Tumor Cells, Cultured; Tumors of the respiratory system and mediastinum; Wound Healing; Human; Lung disease; Respiratory disease; Enzyme; Transferases; Lung cancer; Akt protein kinase; Homology; Malignant tumor; Carcinogenesis; 1-Phosphatidylinositol 3-kinase; Binding protein; Actin; Bronchus disease; Ras gene
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-05-1507

Gene expression profile analysis of non-small cell lung cancers (NSCLC) and subsequent functional analyses revealed that human ANLN, a homologue of anillin, an actin-binding protein in Drosophila, was transactivated in lung cancer cells and seemed to play a significant role in pulmonary carcinogenesis. Induction of small interfering RNAs against ANLN in NSCLC cells suppressed its expression and resulted in growth suppression; moreover, treatment with small interfering RNA yielded cells with larger morphology and multiple nuclei, which subsequently died. On the other hand, induction of exogenous expression of ANLN enhanced the migrating ability of mammalian cells by interacting with RHOA, a small guanosine triphosphatase, and inducing actin stress fibers. Interestingly, inhibition of phosphoinositide 3-kinase/AKT activity in NSCLC cells decreased the stability of ANLN and caused a reduction of the nuclear ANLN level. Immunohistochemical staining of nuclear ANLN on lung cancer tissue microarrays was associated with the poor survival of NSCLC patients, indicating that this molecule might serve as a prognostic indicator. Our data imply that up-regulation of ANLN is a common feature of the carcinogenetic process in lung tissue, and suggests that selective suppression of ANLN could be a promising approach for developing a new strategy to treat lung cancers.