title: Caveolin-1 silencing arrests the proliferation of metastatic lung cancer cells through the inhibition of STAT3 signaling.
abstract: Cav-1 is an essential structural constituent of caveolae implicated in mitogenic signaling, oncogenesis, angiogenesis, neurodegenerative diseases and senescence. Its role as a tumor suppressor gene or as a tumor promoter seems to strictly depend on cell type and tumor stage/grade. The high expression of Cav-1 in some tumors in vivo, amongst which lung adenocarcinoma, is associated with increased tumor aggressiveness, metastatic potential and suppression of apoptosis. In the present study we investigated the role of Cav-1 in metastatic lung cancer proliferation. Cell lines were from metastatic lesions of lung adenocarcinoma (RAL) and of small cell lung carcinoma (SCLC-R1), in which we found Cav-1 expressed at high levels. Results show that siRNA-mediated down-regulation of Cav-1 caused stable arrest of proliferation in both cell lines. A marked reduction of cyclin D1 and of CDK4 expression was evident in the cells transfected with Cav-1 siRNA and consequently of phospho-Rb on ser(795) and ser(780). Furthermore, a significant decrease of the expression of phosphorylated AKT and of its down-stream effectors phosphorylated ERK and STAT3 was evident. Together, these findings indicate that Cav-1 silencing induces an arrest of human metastatic lung proliferation in vitro by a new inhibitory pathway in lung cancer and provide new insights into the molecular mechanisms underlying the pro-survival and tumor-promoting functions of Cav-1.
authors.affiliation: Department of Experimental Pathology, University of Bologna, Bologna, Italy.
authors.forename: Fabia
authors.initials: F
authors.lastname: Pancotti
authors.forename: Laura
authors.initials: L
authors.lastname: Roncuzzi
authors.forename: Marcello
authors.initials: M
authors.lastname: Maggiolini
authors.forename: Anna
authors.initials: A
authors.lastname: Gasperi-Campani
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000077192:Adenocarcinoma of Lung; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D009362:Neoplasm Metastasis; D051058:Oncogene Protein v-akt / Q000378:metabolism; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction; D055752:Small Cell Lung Carcinoma / Q000235:genetics*
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051058:Oncogene Protein v-akt; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4